V 




Class 
Book. 



&pgliffi .. 



COPYRIGHT DEPOSffi 



J 



PELLAGRA 




Diagrammatic cross section of the spinal cord of a pellagrin, the parts 
in red representing the lesions. 1, central canal; 2, column of Clarke; 
3, tract of Burdach; 4, tract of G-oll; 5, tract of de Lissauer; 6, posterior 
roots. (Procupiu, after Babes.) See page 145. 



'■" 



PELLAGRA 



HISTORY, DISTRIBUTION, DIAGNOSIS, PROGNOSIS, 
TREATMENT, ETIOLOGY 



BY 

STEWART R. ROBERTS, S. M., M. D. 

4 

ASSOCIATE PROFESSOR OP THE PRINCIPLES AND PRACTICE OF MEDICINE, ATLANTA COLLEGE 

OF PHYSICIANS AND SURGEONS, ATLANTA, GEORGIA; PHYSICIAN TO THE WESLEY 

MEMORIAL HOSPITAL; FORMERLY PROFESSOR OF BIOLOGY IN EMORY COLLEGE 



WITH EIGHTY-NINE SPECIAL ENGRAVINGS 
AND COLORED FRONTISPIECE 



ST. LOUIS 

C. V. MOSBY COMPANY 

1912 






^ v ^ 



Copyright, 1912, by C. V. Mosby Company 



Press of 

C. V. Mosby Company 

St. Louis 



£ CI.A314932 



' 



■) 



To THAT LONG LINE OF PHYSICIANS AND SCIENTISTS FROM 
Casal THROUGH Lombroso TO Sambon, AND THOSE WHO 

SHALL COME AFTER THEM WHO HAVE BEEN AND ARE AND SHALL 
BE STUDENTS OF PELLAGRA, 

THIS VOLUME IS DEDICATED BY 
THE AUTHOR, 

WITH THE HOPE THAT THE DAY IS NOT FAR DISTANT WHEN 

THERE SHALL ARISE FROM AMONG THEM ONE TO WHOM SHALL 

BE REVEALED WITH CLEAR AND CERTAIN PROOF THE TRUE 

CAUSE OF THE MAL DE LA ROSA. 



PREFACE. 

This is a book on Pellagra for the student and the practicing phy- 
sician. It is not merely a discussion of Pellagra, nor is it devoted 
to upholding any special theory of etiology. 

At the present time it is impossible to have a book of this size 
contain the entire data concerning the disease. It is not only im- 
possible to include all such matter, but it would be also useless. We 
need the essential facts of the subject — we need to know its pathol- 
ogy, its diagnosis, and its treatment. There has been entirely too 
much speculation on Pellagra, and entirely too little investigation 
of Pellagra. 

It is a pleasure to express my thanks to all those who have studied 
and written extensively on the disease. Among these are Casal, the 
elder Strambio, Jansen, Frapolli, Lombroso, Roussel, Hirsch, Sam- 
bon, Marie, and the contributors to the National Pellagra Congress 
of 1910. Other acknowledgments are made throughout the book. 
I wish to thank Dr. Eugenio Bravetta, of Mombello, province of 
Milan, for many photographs, and especially for his aid in the study 
of his pathological sections, for the preparation of which he deserves 
much credit. 

I am particularly indebted to Dr. E. M. Green, clinical director 
of the Georgia State Asylum for Insane at Milledgeville, for per- 
mission to use his valuable work and classification on "Psychoses 
Accompanying Pellagra," and to Dr. S. S. Hindman, pathologist 
to the same institution, for permission to use his report on the 
cerebrospinal fluid. 

The chapter on Alimentary Tract in Pellagra includes the re- 
searches of Dr. J. Clarence Johnson, of Atlanta, on the digestive 
system, and I wish to acknowledge my thanks to him for his aid in 
the preparation of this chapter. 

My thanks are due to Dr. Charles C. Bass, of New Orleans, for 
photographs, and to Dr. J. 0. Elrod, of Forsyth, Georgia, and to 
many others for valuable aid. Mrs. M. L. Ragin, my secretary, 

7 



8 PREFACE. 

has been of much assistance in the preparation of the manuscript 
and the index. 

Finally, I wish to express my gratitude to one whose mature wis- 
dom and kindly approval are always a source of constant help and 
encouragement. 

Stewart R. Roberts. 
Atlanta, Ga., May, 1912. 



WORDS OF GOETHE. 

The following, written by the poet Goethe in his " Italian Jour- 
neys ' (from Brenner, in the Tyrol, Austria, to Yerona, Italy), 
September, 1786, is of peculiar interest in connection with the now 
supposed etiology of Pellagra: 

I know little, if anything, pleasing to say about the people. As soon as 
the sun rose over the Brenner paths in the Alps I noticed a decided change in 
their appearance, and especially displeasing to me was the brownish tan color 
of the women. Their features indicated misery, and the children were just as 
pitiful to behold; the men are little better, though their general features were 
regular and good. 

I believe the cause of this sickly condition is found in the continued use of 
Turkish and heath corn. The people call the Turkish corn also yellow grain 
and the heath corn black grain. These are ground, the meal mixed with 
water, cooked to a thick paste, and eaten in this condition. The Germans 
across the Alps divide the dough into small pieces and fry it in butter. The 
Tyrolese, on the other hand, eat it plain, sometimes with cheese on it, but eat 
no meat the entire year; besides this, they eat fruit and green beans, which 
they soak in water and cook with garlic and oil. 



CONTENTS. 



CHAPTER I. 

PAGE 

General Considerations 17 

Pronunciation — Typical cases — Definition — Description — Age — 
Sex — Inheritance — Contagion — Immunity — Occupation. 

CHAPTER II. 

History and Geogeaphical Distribution 43 

Synonyms — History — Geographical distribution — Spain — Italy — 
France — Egypt — America. 

CHAPTER III. 

Classification 74 

A general disease — Other infections in pellagra — Relation to the 
seasons — Incubation period — Duration — Duration of a single at- 
tack — Acute pellagra — Subchronic pellagra — Chronic pellagra — 
Stages of chronic pellagra — Pellagra sine exanthemate — Pseudo- 
pellagra. 

CHAPTER IV. 

Alimentary Tract in Pellagra 107 

The tongue — Gums — Teeth — Buccal mucosa — Palate — Salivary 
glands — Pharyngitis — Esophagitis — Stomach and intestines — 
Tissue changes. 

CHAPTER V. 

Skin in Pellagra 121 

Character — Pellagrous skin — Dimorphous — Classification — Loca- 
tion — Relation to light — Sensory symptoms — Changes in the 
skin. 

CHAPTER VI. 

Xeryous System in Pellagra 142 

Introduction — Tissue changes in brain and cord — Relation of cord 
lesions and clinical symptoms — Sympathetic nervous system — 
Cerebrospinal fluid — Examination of cerebrospinal fluid — Pain 
— Reflexes — Changes in the muscular system — Insomnia — Head 
symptoms — Neurasthenic state — Mental state — Psychoses accom- 
panying pellagra. 

11 



12 CONTENTS. 



CHAPTER VII. 

PAGE 

Other Systems and Changes ,185 

Circulatory system — The blood — Pulse — Blood pressure — No in- 
fecting agent found — Tissue changes — Lungs — Temperature — 
Bones — Weight — Genito-urinary system — Urine — Sexual organs 
and functions — Organs of special sense — Eye — Ear — Taste — 
Touch — Smell.' 

CHAPTER VIII. 

Diagnosis and Prognosis 204 

Diagnosis of pellagra — During the period of onset — During the at- 
tack — During the intermission between attacks — Pellagra sine 
exanthemate — Prognosis in pellagra. 

CHAPTER IX. 

Treatment of Pellagra 218 

Treatment of avail — Improvement — Associated infections — Treat- 
ment of disease — Medicinal treatment — Salvarsan in pellagra — 
Chlorides — Transfusion — Diet — Hygienic measures — Baths — 

— Climate — Treatment of special symptoms — Dermatosis — Diar- 
rhea — Stomatitis — Nervous system. 

CHAPTER X. 

Cause of Pellagra 231 

Cause unknown — Many different theories — Two chief theories — 
Pellagra an intoxication — Varieties of corn — Analyses of corn 

— Corn in Italy — Good corn the cause — Spoiled corn the cause — 
Argument for and against corn — Pellagra an infection — Patho- 
logical evidence — Ecological evidence — An insect agent — Simu- 
lium fly — Argument for and against an infection — Summary of 
theories — Outlook. 



ILLUSTRATIONS. 

Diagrammatic cross section of the spinal cord of a pellagrin . . Frontispiece 

fig. page 

1 Pellagrous boy, showing dermatitis on hands and face .... 24 

2 Dermatitis on hands of pellagrin 34 

3 Dermatitis on feet of pellagrin 36 

4 Map showing distribution of pellagra in the western half of the 

state of Tennessee 54 

4a Map showing distribution of pellagra in the eastern half of the state 

of Tennessee 55 

5 Map showing distribution of pellagra in the United States . . .56,57 

6 Pellagrosario at Rovereto, Austria 65 

7 Group of eight boys, all pellagrins 70 

8 Closer view of three of the boys shown in Fig. 7 ....... 70 

9 Map showing distribution of pellagra in the world 72,73 

10 Pellagrous boy 75 

11 Two Georgia cases, presented by the State Hookworm Commission . 76 

12 Same case as Fig. 11, side view 76 

13 Diagram illustrating periods in an attack 86 

14 Pellagra during period of attack 87 

15 Diagram illustrating stages of chronic pellagra with relation to clin- 

ical symptoms 97 

16 Intestines, showing atrophy of the muscles 114 

17 Section of liver 118 

18 Spleen, showing increase in connective tissue 119 

19 Dermatitis on hands 122 

20 Diagram illustrating the development and course of pellagrous der- 

matitis 123 

21 Insane pellagrin 124 

22 Pellagrous dermatitis 125 

23 Dermatitis 127 

24 Italian case of senile hands in pellagra 131 

25 Wet form of dermatitis 134 

26 Rough hands of a pellagrin as contrasted with the normal hands of 

a hospital orderly 135 

27 Italian case of typical dermatitis 136 

28 Pellagrous dermatitis 137 

29 Georgia case, showing exfoliation of the skin following a spring at- 

tack 138 

30 Italian case of alcoholic erythema 139 

31 Italian case of alcoholic erythema 139 

13 



14 ILLUSTRATIONS. 

FIG. PAGE 

32 Close view of the rough skin in pellagra . . 140 

33 Pellagrous dermatitis 141 

34 Cortical cells, showing pigmentary degeneration 143 

35 Cortical cell, showing contraction of the protoplasm 144 

36 Cells from the spinal cord, showing thickening and contraction of the 

neuro-fibrillar net 144 

37 Cells from the spinal cord, showing partial thickening and contrac- 

tion of the neuro-fibrils 145 

38 Cell from spinal ganglion, showing pigmentary degeneration . . 146 

39 Chromatolysis and pigmentary degeneration in cells of the cord . . 147 

40 Same case as Fig. 35, showing chromatolysis and pigmentary de- 

generation in cells of the cord 147 

41 Cells from the cord, showing yellow pigmentation and degeneration . 148 

42 Same case as Fig. 37, showing cells from the cord, with yellow pig- 

mentation and degeneration 148 

43 Spinal cord, showing the cellular body entirely invaded by yellow 

globular pigment 149 

44 Spinal cord, showing the cell partially invaded by yellow globular 

pigment 149 

45 Cell is invaded in two opposite places by yellow globular pigment . 150 

46 Partial thickening of the neuro-fibrillar net 150 

47 Spinal cord, showing pigmentary granular degeneration . . . . 151 

48 Spinal ganglia, showing invasion of the special net or Marinesco's 

net 152 

49 Spinal cord, showing thickening and concentration of the neuro- 

fibrillar net 153 

50 Spinal ganglia, showing changes in the fibrillar net 155 

51 Spinal cord, showing increase in the neuroglia in crossed, pyramidal 

tract 157 

52 Spinal cord, showing section of Burdach's tract, with several fibers 

and primary degeneration 158 

53 Spinal cord, showing section of Burdach's tract, with numerous fibers 

in secondary degeneration 159 

54 Pellagrous insanity, showing dermatitis on hand, with exfoliation 

of the skin 167 

55 Pellagrous insanity, showing dermatitis on hands 169 

56 Pellagrous insanity, showing dry dermatitis, with exfoliation of the 

skin 173 

57 Pellagrous insanity in the aged .175 

58 Pellagrin, with dermatitis on hands, forearms, and elbows . . . 187 

59 X-ray illustration of the hands of a female pellagrin 194 

60 X-ray illustration of the hands of a female pellagrin 195 

61 Same case as Fig. 60, showing x-ray illustration of the cervical re- 



gion 



196 



62 Pellagrin after recovery from attack - . 210 

63 Pellagra in time of intermission 212 



ILLUSTRATIONS. 15 

FIG. PAGE 

64 Same case as Fig. 63, showing elbow slightly rough; hands appear 

normal, but covered with fine branny scales 213 

65 Field- of Italian corn, first crop 237 

66 Field of Italian corn, first crop 238 

67 Field of Italian corn, second crop 239 

68 Ear of Italian corn, first crop 240 

69 Ends of three ears of Italian corn, first crop 241 

70 Method of drying shelled corn in Italy 242 

71 Corn swept into another kind of building after drying in the sun . 243 

72 Cakes of yellow polenta 244 

73 American corn from Georgia 244 

74 American corn from Georgia 245 

75 Field of American corn, Georgia 245 

76 One method of gathering and drying corn in America 246 

77 Rail pens without covers, sometimes used for storing unshucked corn 

in America 246 

78 Cribs used for drying corn in the United States 247 

79 Diagrammatic section of a grain of corn 248 

80 Cellular structure of a grain of corn 250 

81 Penicillium, a common mold found on corn 251 

82 Ustilago maydis, a fungus that causes corn smut 252 

83 Simulium fly and larva 252 

84 Wing of simulium fly, showing venation 252 

85 Legs of a chicken showing pellagrous symptoms 254 

86 Legs of a chicken showing similar symptoms to those of chicken in 

Fig. 85 255 

87 Bobbin Creek, near Athens, Ga., where the simulium larva? were first 

found in Georgia 256 

88 Diagram showing pellagrous neighborhood at Dadeville, Ala., and the 

relation of pellagra to streams 258 

89 Diagram showing the relation of pellagra to streams in the town of 

Cornelia, Ga 259 



PELLAGRA 



CHAPTER I. 

GENERAL CONSIDERATIONS. 

The manifestations of pellagra are definite only in wide limits. 
One case may be as different from another case as if each were a 
different disease. It is well, therefore, for the student of pellagra 
to note the varying and different symptoms of several typical cases, 
each case differing in course and severity from the others. 

PRONUNCIATION. 

Pellagra is pronounced in the United States in three ways. It is 
called (1) peTla-gra — e short as in fell, first a short as in am, second 
a broad as in father, with the accent on the first syllable; (2) pel- 
la'gra — each a long as in fate, with the accent on the second syllable ; 
(3) pel-la/gra — each a broad as in father, with the accent on the 
second syllable. Dictionaries are presumably correct, but even they 
differ in the pronunciation of this Avord. It is an Italian word, 
originated among the common people of Italy, and was first used 
in medical literature by Frapolli in 1771 in the phrase, "morbus 
vulgo pellagra/' meaning "a disease among the people called 
pellagra." The name is therefore of peasant origin, and is a union 
of two Italian words — pelle, meaning skin; agro, meaning rough. 
The final e before another vowel is dropped, the final o of agro is 
changed to a; thus pelle agro becomes pell -j- agra, or the present 
word pellagra, meaning rough skin. 

In the Italian language the word is pronounced pel-la'gra, each 
syllable separately and distinctly spoken, the accent on the second 
syllable, and each a pronounced broad as in father. This Italian 
pronunciation differs from all three used in America in that the 
Italians use I separately in the first two syllables, while in Amer- 
ica the word is pronounced as if it were spelled with only one I. 
It is manifestly out of the question to pronounce it as the Italians 
do, and therefore the word has been Anglicized and is now an Eng- 
lish word, and to be pronounced according to English methods. 

17 



18 PELLAGRA. 

Webster gives pe-la'gra, but prefers pe-la'gra; the Century dic- 
tionary gives only one pronunciation — pe-la/-gra. Webster's pref- 
erable pronunciation is not used at all in this country, and, since 
both dictionaries give pe-la'gra, and, in addition, the other two 
related words — pella/grin and pella/grous — are pronounced with the 
a long and accented second syllable, as pe-la/grin and pe-la/grus, it 
seems wise to use this altogether natural and easy American pro- 
nunciation, pe-la'gra. 

TYPICAL CASES. 

One need not expect to find a typical pellagra. It is a disease 
of many symptoms and of many variations ; its only consistency is 
its inconsistency ; it seems cured and yet recurs ; the pellagrin seems 
to be approaching his end and yet lives for many years ; it spreads 
and is not contagious; the offspring of the pellagrin receives his 
mark and yet it is not inheritable ; it is not and appears ; it is and 
disappears ; it is a morbid entity and yet it contains within itself 
many lesser morbid entities ; it falls with equal right in the sphere 
of dermatology, neurology, and gastrology, and yet it is a general 
disease ; divers diseases become one, and this one is called pellagra ; 
there is no pellagra — only the pellagrous. 

The following cases are selected with a view of illustrating differ- 
ent pictures of the same disease in reference to severity, marked 
improvement, early death, pellagra in the negro, termination in in- 
sanity, and general clinical symptoms common to pellagrins. It is 
well to understand and keep in mind the general picture of the 
disease, but it is well also to remember that this picture is a com- 
posite picture, made up of widely different and apparently unre- 
lated pictures, imposed one upon the other in all imaginable angles, 
and each individual picture, as well as the composite result, vary- 
ing in hue and aspect in each case and in every season. No disease 
is so plain as pellagra in the early spring, and no disease so obscure 
as pellagra in the same patient in midwinter; a slight indigestion 
may introduce the pellagrous attack, and the case be so slight in its 
systemic effect that a month later no apparent traces remain. 

Case 1. 

A housewife, aged 48, the mother of nine children, noticed that 
for the past month she had not been feeling as well as usual. Up 



GENERAL CONSIDERATIONS. 19 

to this time she had always been an exceptionally healthy woman. 
She married at 17, lived in the mountains of North Georgia until 
grown, and has lived in the country all her life. She had always 
done her own .work ; her labors had been very easy and without 
complications; no miscarriages, and her menstrual period regular 
until the last period, which did not appear. Her husband is living, 
and her children are healthy. 

About May 1st her appetite began to fail, and there gradually 
developed a feeling of uneasiness in the stomach, which at times 
amounted almost to nausea. There seemed to be an increased 
amount of gas in the intestines, although she did not belch at all. 
There was no pain in the abdomen or anywhere else, and she at- 
tributed her trouble to "biliousness and indigestion," but noticed 
that her indigestion seemed to continue, whether she ate or not. 
The uneasiness in the abdomen was neither made worse nor better 
by food. About this time a diarrhea began to develop, and she 
would have from four to eight thin stools daily, but did not pass 
any blood. These movements had a peculiar odor like oats or 
barley after soaking in water. 

She did not feel very weak, but thought her clothes hung rather 
loosely, and imagined she was losing a little flesh. About this 
time she noticed a peculiar discoloration on the back of her hands, 
and thought at first they were sunburned, though she could not 
remember being in the sun long enough to have caused this. This 
color on her hands ended just above the wrists ; it did not hurt her, 
though when she used hot water to wash the dishes her hands 
seemed tender and sensitive. 

She had come very near having headache. She had strange 
feelings in her head, as if something were about to happen, and if 
she stood up quickly she felt slightly dizzy. Her husband thought 
she was rather nervous, and she cried easily for seemingly no 
reason. 

On examination she gave one the impression of having great 
weariness, and seemed glad of an opportunity to lie down. The 
palms of her hands were normal, but on the backs the skin was of a 
deep sunburn, with a peculiar brown tint added. It was symmet- 
rical on both hands, extended from above the wrists to about the 
middle of the fingers, and the skin over the first phalangeal joints 
was loose and unduly wrinkled. In the middle of the back of one 
hand the skin was beginning to peel off, leaving a thin new skin 



20 



PELLAGRA. 



beneath slightly lighter in color than the old. Her hands looked 
thin, and the fingers rather long drawn out. Her elbows w T ere 
rough and the skin loose. 

Her tongue was without a coat — red, with a few little fissures 
about the middle; the inside of the cheeks was red and tender, 
and her whole mouth sore. Heart and lungs negative; abdomen 
negative, except for the presence of large amount of gas in the 
intestines. Knee jerks equal and slightly exaggerated; eyes nor- 
mal ; no ataxia, no ankle clonus, or Babinski reflex. Pulse, 90 ; 
temperature, 98 ; respiration, 18. Urine averaged 30 ounces in 
twenty-four hours; specific gravity, 1.005; no albumen, sugar, or 
casts; a few blood and epithelial cells. Blood normal, except 
hemoglobin, 80 percent. "Weight, 135. 

She was put in bed for a few days, and then allowed to sit up 

Table Showing the Varying Conditions of Case 1. 







Tem- 




Res- 






Tem- 




Res- 


Date. 


Hour. 


pera- 
ture. 


Pulse. 


pira- 
tion. 


Date. 


Hour. 


pera- 
ture. 


Pulse. 


pira- 
tion. 


June 6 


11 a. m. 


102 


114 


18 


June 20 


8 a. m. 


981 


80 


18 





1 p. m. 


10H 


98 


20 


20 


4 p. m. 


98,1 


88 


16 


6 


3 p. m. 


1021 


94 


20 


21 


8 a. m. 


98 


80 


20 


6 


6 p. in. 


101 


92 


18 


21 


4 p. m. 


981- 


82 


18 


7 


8 a. in. 


100 


90 


20 


22 


8 a. m. 


98 


80 


18 


7 


4 p. m. 


99 


94 


26 


22 


4 p. m. 


981 


78 


18 


8 


8 a. in. 


98,1 


90 


18 


23 


8 a. m. 


98 


92 


20 


8 


4 p. m. 


99 


82 


24 


23 


4 p. m. 


981- 


72 


18 


9 


8 a. m. 


99 


90 


24 


24 


8 a. m. 


98,1 


80 


18 


9 


4 p. m. 


98-1 


100 


18 


24 


4 p. m. 


99 


99 


20 


10 


8 a. m. 


971- 


78 


18 


25 


8 a. m. 


981 


100 


22 


10 


4 p. m. 


981 


92 


14 


25 


4 p. m. 


991 


100 


20 


11 


8 a. in. 


98 


90 


20 


26 


8 a. m. 


98 


98 


16 


11 


4 p. m. 


99 


84 


18 


26 


4 p. m. 


981 


86 


18 


12 


8 a. in. 


99 


80 


20 


27 


8 a. m. 


97-1 


82 


16 


12 


4 p. m. 


981 


86 


14 


27 


4 p. m. 


991 


86 


16 


13 


8 a. in. 


98 


96 


18 


28 


8 a. m. 


981 


90 


18 


13 


4 p. m. 


98-1 


78 


18 


28 


4 p. m. 


99 


76 


20 


14 


8 a. m.. 


98 


90 


16 


29 


8 a. m. 


98 


82 


16 


14 


4 p. m. 


98,1 


86 


16 


29 


4 p. m. 


98-1 


92 


16 


15 


8 a. in. 


98-1 


100 


16 


30 


8 a. m. 


99,1 


80 


16 


15 


4 p. m. 


99-1 


88 


16 


30 


4 p. m. 


99 


82 


18 


16 


8 a. m. 


981- 


100 


16 


July 1 


8 a. m. 


99 


88 


16 


1G 


4 p. m. 


99 


98 


14 


1 


4 p. m. 


994 


92 


18 


17 


8 a. m. 


93 


88 


14 


2 


8 a. m. 


99 


88 


16 


17 


4 p. m. 


981 


100 


16 


2 


4 p. m. 


99 


84 


18 


18 


8 a. m. 


981 


80 


20 


3 


8 a. m. 


99,1 


88 


18 


18 


4 p. in. 


98 


88 


16 


3 


4 p. m. 


991 


80 


18 


10 


8 a. m. 


981 


99 


20 


4 


8 a. m. 


98-1- 


80 


18 


19 


4 p. m. 


99 


83 


18 













GENERAL CONSIDERATIONS. 21 

at intervals. Her diet was rather full, with the exception of 
pastries and heavier vegetables, and she was given milk and albu- 
mens between meals and at bedtime. Fowler's solution was given, 
beginning at 3 drops and increasing gradually to 10, three times 
a day. She was encouraged, and seemed better on the days her 
friends and relatives visited her. She grew better rapidly, gained 
in strength and flesh, and was discharged on the twenty-ninth day 
apparently in good health and with a gain of 8 pounds. 

The interne at the hospital marked this case "cured" on the 
records, much to the displeasure of the head nurse. I heard a 
month later that the woman was improving, but had at times 
slight attacks of diarrhea. 

Discussion of Case 1. 

This case illustrates the first attack of pellagra in a previously 
healthy woman of middle age. Notice that she lived in the country, 
and that digestive disturbances ushered in the attack. Without 
the bilaterally symmetrical erythema, the diagnosis might have 
been incorrect. The nervous and cutaneous symptoms were sub- 
ordinate to the digestive disturbances and the diarrhea. The pulse 
was fast and the temperature slightly below normal; the urine of 
low specific gravity. She lost flesh, seemed tired, and appreciated 
encouragement. The only medicine used was a form of arsenic. 

Case 2. 

A widow, aged 30, no children, complains of pains all over her 
body, and a diarrhea that comes every three months for about three 
days. Her pains are worst in the waist line. Her family history 
is negative. In childhood she had measles, whooping-cough, and 
chicken-pox. She had good health until her husband died in 
March, 1904, and grief over his death brought on an attack of 
nervous exhaustion. She had a similar attack three years later. 
In 1908 she was operated on for appendicitis and a movable right 
kidney double in size. This right kidney is still very sensitive. 
She felt bad in the spring of 1908 for tAvo or three months, but im- 
proved after going to the mountains. This sensation of being weak 
and run down recurred in the springs of 1909 and 1910. She im- 
proved each time after going to the mountains, but now, August, 
1910, there is a recurrence of these spring attacks, this one more 
severe than ever before. 



22 



PELLAGRA. 



She is constipated at the present time, sleeps poorly, and has a 
good appetite. Her menstrual period has been irregular, and has 
not appeared for the last three months. She has suffered two nerv- 
ous breakdowns in the last six years, both of them occurring in the 
spring of the year. She is now very irritable and nervous. She 
is a highly educated woman, and was formerly in the habit of 

Table Showing the Vaeying Conditions of Case 2. 







Tem- 




Res- 






Tem- 




Res- 


Date. 


Hour. 


pera- 
ture. 


Pulse. 


pira- 
tion. 


Date. 


Hour. 


pera 
ture. 


Pulse. 


pira- 
tion. 


Sept. 22 


8 a. m. 


99 


102 


18 


Oct. 8 


12 m. 


100* 


126 


24 


22 


4 p. m. 


99 


84 


20 


8 


4 p. in. 


101 


132 


24 


23 


8 a. m. 


98 


90 


18 


8 


8 p. in. 


102 


134 


26 


23 


4 p. m. 


99 


102 


26 


8 


11 p.m. 


101* 


142 


26 


24 


8 a. m. 


98 


98 


24 


9 


3 a. m. 


102* 


140 


28 


24 


4 p. m. 


98 


96 


24 


9 


8 a. in. 


101* 


132 2 


26 


25 


8 a. m. 


98 


102 


24 


9 


12 m. 


100* 


128 


18 


25 


4 p. m. 


98 


70 


1 26 


9 


4 p. m. 


100 


134 


26 


26 


8 a. m. 


98 


90 


20 


9 


8 p. m. 


102 


130 


22 


26 


4 p. m. 


99 


102 


20 


9 


10 p. in. 


102 


140 


26 


27 


8 a. m. 


99 


108 


20 


10 


2 a. m. 


102* 


120 


22 


27 


4 p. m. 


99 


100 


24 


10 


8 a. m. 


100* 


120 


20 


28 


8 a. m. 


98 


100 


24 


10 


12 m. 


102 


134 


28 


28 


12 m. 


99 


108 


16 


10 


4 p. m. 


102 


130 


28 


28 


4 p. m. 


99 


100 


18 


10 


8 p. in. 


101* 


134 


26 


29 


8 a. m. 


99 


100 


20 


10 


12 p. in. 


102 


126 


26 


29 


4 p. m. 


99 


102 


20 


11 


8 a. m. 


101* 


140 


30 


30 


8 a. m. 


98 


100 


20 


11 


12 m. 


101 


132 


28 


30 


4 p. m. 


99 


108 


20 


11 


4 p. m. 


101 


124 


30 


Oct. 1 


8 a. m. 


98 


98 


18 


11 


8 p. m. 


102 


120 


30 


1 


4 p. m. 


99 


108 


22 


11 


12 p. m. 


101* 


126 


30 


2 


8 a. m. 


99 


130 


20 


12 


2 a. m. 


100 1 


120 


30 


2 


4 p. m. 


99 


120 


24 


12 


8 a. m. 


98* 


124 


22 


3 


8 a. m. 


99 


126 


24 


12 


12 m. 


102 


112 


26 


3 


4 p. m. 


100 


130 


24 


12 


4 p. m. 


100* 


120 


28 


4 


8 a. m. 


99 


130 


28 


12 


6 p. m. 


103 


130 


34 


4 


4 p. m. 


99i 


120 


26 


12 


10 p. m. 


103 


140 


32 


5 


8 a. m. 


101* 


128 


30 


13 


1 a. m. 


103 


140 


19 


5 


4 p. m. 


102 


150 


28 


13 


5 a. m. 


104 


140 


20 


6 


8 a. m. 


103 


120 


24 


13 


8 a. m. 


104 




22 


6 


4 p. m. 


103 


140 1 


30 


13 


4 p. m. 


103 


128 


24 


7 


8 a. m. 


101 


128 


22 


13 


8 p. in. 


103 


140 


28 


7 


10 a. m. 


100* 


120 


26 


13 


12 p. m. 


103* 


i40 


32 


7 


4 p. m. 


101* 


150 


26 


14 


2 a. in. 


104* 




22 


7 


7 p. m. 


102 


148 


26 


14 


8 a. in. 


103 3 


130 


28 


8 


1 a. m. 


102|- 


128 


22 


14 


12 m. 


104 




26 


8 


8 a. in. 


101 


120 


20 


14 


9 p.m. 4 









1 Direct transfusion. 

2 Direct transfusion. 

3 Axilla. 

* Patient expired. 



GENERAL CONSIDERATIONS. 23 

reading a great deal. She has noticed a gradual failure in her 
memory and ability to understand what she reads. At present it 
is often necessary for her to read the same sentence or paragraph 
over two or three times before she can understand it, and she has 
difficulty in remembering even the simplest things. 

Her weight three years ago was 100 pounds; now 86. She is a 
tired, nervous-looking woman, with little strength. She gives one 
the impression of exhaustion and rapidly approaching cachexia. 
On September 13, 1910, she is nervous and suffers with abdominal 
uneasiness from no apparent cause that she knows. The entire 
dorsum of both hands is rough, scaly, cracked in places, especially 
over the knuckles, and the dorsum of the wrists presents the same 
appearance, the whole area having a light-russet tint. Over the 
knuckles the soreness is more severe; a little serum exudes from 
the raw surface of the fissured skin, and above the erythematous 
area on the forearms the skin is rough up to and including the 
elbow on the extensor surface. This erythema and roughness is 
symmetrical on both sides. 

Between the fingers on the back the brown tint changes to a 
pink or red, and the tips of the fingers on the palmar surface seem 
unusually pink and clean. The skin on the back seems to be peel- 
ing in places, and a skin lighter in color, but still pigmented, 
appears beneath. The skin of the erythematous area is rather 
glistening, thin, and dry, and scales are larger than the bran-like 
scales of the nonerythematous area above the wrist. The forehead 
is slightly rough, although not enough to be apparent without 
very close examination. There is some atrophy of the hands, and 
the skin is looser than normal. 

The heart and lungs are negative ; gas is present in large amounts 
in the intestines, and the abdomen has a peculiar appearance as if 
about to point at the umbilicus. She thinks her hands are swollen 
at times, especially after a restless, sleepless night. Her reflexes 
are all exaggerated ; no ankle clonus or Babinski reflex. Her mind 
is noticeably slow and dull ; it is an effort for her to answer a ques- 
tion at all; the introduction of a new subject causes an effort on 
her part to incorporate it into the stream of her consciousness, and 
she gives the impression of abject neurasthenia, with a tendency to 
melancholia. 

Her height is 5 feet 1 inch. Pulse, 96 ; temperature, 99.5 ; 
urine, 1.005 ; acid, no albumen or sugar, and the microscope shows 



24 



PELLAGRA. 



nothing abnormal. Hemoglobin is 75; reds, 4,602,950; whites, 
9,400. Stomach contents after test meal showed 190 cc, free 
HC1 .15 percent ; total acidity, .33 percent. 





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Fig. 1. — Pellagrous boy. Dermatitis on hands and face. Austrian case. (After Merk.) 

The diagnosis is, of course, pellagra of possibly six years' dura- 
tion. She is apparently in the stage of cachexia, and the outlook 
is bad. She became gradually worse; nausea, vomiting, and diar- 
rhea increased, and pulse rose to 130; temperature, 99.3°. On 



GENERAL CONSIDERATIONS. 25 

October 9th, four days before her death, examination of blood 
showed hemoglobin of 70 percent; reds, 2,780,000; whites, 6,970. 
Differential count: polynuclears, 57 percent; lymphocytes, small, 
24 percent; large, 16 percent; eosinophiles, 3 percent. Her 
fever and pulse continued to rise, great quantities of bile-stained 
fluid were vomited, gas in the abdomen increased, abdomen dis- 
tended, bowel movements of a quart of pure watery discharge. 
Dissolution on October 13th, with temperature in axilla of 104.3° 
just before death. 

Discussion of Case 2. 

This is a case of recurrence for six successive years, reaching 
finally cachexia, with rapid death. The trouble was not diagnosed 
until two months before her death. The erythema was present in 
August. The blood showed excess of lymphocytes. The mental 
symptoms were not as severe as one would have supposed from 
the physical condition. Rest, treatment, arsenic, and transfusion 
were of no avail. The rapidity of the pulse was out of all propor- 
tion to the temperature. During the last month the blood lost red 
corpuscles rapidly, but the hemoglobin remained nearly the same. 

Case 3. 

A married woman, aged 25, with one healthy child 3 years old, 
was seen on June 24, 1911. Her father died of paralysis at 56, 
and her mother is living and well, 52 years old. She has always 
lived within one hundred yards of a branch and half a mile of a 
creek all her life, and has eaten corn bread in usual amounts. For 
the past five years she has been especially nervous at her menstrual 
period, and she does not think her nervous system is in a good con- 
dition. During this time her health was bad every spring, extend- 
ing even into midsummer. During these spring attacks she noticed 
she grew weak and had some dizzy feelings, but thought she had 
the "spring fever." During the spring of 1910, with the usual 
spring weakness, she had a slight stroke of paralysis; and her 
whole left side has been of little use in work since. Her menstrual 
period is regular, but scanty; no pain, except backache at times. 
She has never had any diarrhea, and is usually constipated. 
Lately there has been a feeling of dullness in her head, almost 
headache, and she grows despondent and cries at times. 

There is evidence of a right hemiplegia, slight hemiplegic gait, 



26 PELLAGRA. 

left knee jerk absent, and slight ankle clonus in left foot. Right 
knee jerk slightly exaggerated. Her usual weight is 135, but she 
has lost 8 pounds this spring. She looks weak, though well 
nourished. Her face is sad. Pulse, 90 ; temperature, 99.4 ; tongue 
slightly coated in middle, sore and red at tip and margins. Blood 
pressure, 85 mm. One month ago her mouth was sore and raw 
inside; gums and inside of lips still red; throat red. She has too 
much gas in the abdomen, though her appetite is good, and there 
has been no nausea. Three weeks ago the backs of her hands grew 
red, and she thought they were sunburned ; the skin from the middle 
of the fingers to above the wrists then began to peel off in scales 
and at times she felt burning sensations in her hands and feet. 
Her hands now are rough and cracked slightly, of a sepia tint, the 
finger tips pink and clean. Blood shows hemoglobin 85 percent; 
urine with a specific gravity of 1.012, otherwise negative. Heart, 
lungs, and abdomen negative. 

Discussion of Case 3. 

This case illustrates a pellagra of probably five years' standing, 
no diarrhea, no nausea, and a slight hemiplegia, probably of pella- 
grous origin. This case might have been diagnosed as a chronic 
neurasthenic, and indeed I suspected neurasthenia, when I first saw 
her, from her general appearance. The erythema clinched the 
diagnosis of pellagra. There was no great inroad made on the 
general nutrition; even her periods continued. She had probably 
had the erythema before, though had never noticed it until this 
last attack. This type corresponds more to the chronic form com- 
mon in Italy. Notice the burning in her hands and feet. 

Case 4. 

A farmer, aged 50, the son of pellagrins, was seen in August. 
He had an attack of pellagra in the spring of 1910, with a recur- 
rence the following September. In the spring of 1911 there was a 
third attack, this time more severe than in the preceding year. 
Since March he seemed to grow worse rapidly. He lost 40 pounds ; 
his memory became bad, and his mind almost a blank. He was 
brought to the hospital a month ago suffering with acute confu- 
sional insanity, difficulty in speech, cachectic, and helpless. 

His tongue is without a coat, bald, red like a cut beet, and cov- 
ered with small fissures. The erythema extends from the middle 



GENERAL CONSIDERATIONS. 27 

of the second phalanx half way up the forearm to the elbow on 
the extensor surface, and around the wrist, meeting on the flexor 
surface. All this erythematous area is peeling and cracking; the 
hands are thin and bony; the fingers long and keen. Above the 
eruption the skin is rough and scaly ; this roughness extends up on 
the shoulders, and even appears on the trunk, forehead, and as 
scaly patches below and behind each ear. Erythema on ankles, 
half way up leg to knee ; knee rough and scaling. The elbows are 
exceedingly rough, almost like an ichthyosis. His lower legs some- 
what spastic, and he is unable to control them. Before he became 
bedridden he was ataxic; would fall at times, and often stagger 
when walking. 

His entire left side presented a striking contrast with the right. 
On the left he had ankle clonus, Babinski reflex, trophic disturb- 
ances of the left hand, fingers slightly swollen at the tips; the 
nails white, thick, long, and swelling at base and beneath, with 
contractures of fingers — a claw hand. Knee jerks greatly exag- 
gerated, eyes glassy and staring. 

He was put in bed and showed marked improvement from the 
beginning of treatment. He was fed four times daily, chiefly on 
meats, milk, cheese, salads, a few vegetables. He was given iron, 
quinin, and strychnin, Fowler's solution in increasing doses, and 
occasionally tincture of nux vomica. A month after treatment 
began he was growing stronger, had a good appetite, and could 
talk a little, though his ideas were still confused. He will prob- 
ably continue to improve until next spring, though confirmed 
dementia may develop. 

Discussion of Case 4. 

This case illustrates the rapid onset of cachexia and insanity in 
a man ; trophic changes in the hand ; wide distribution of the rough 
skin; marked improvement after cachexia had begun; ataxia, and 
spastic condition of lower extremities. The spinal cord was, of 
course, markedly affected, and the nervous symptoms predominated. 
Diarrhea was almost absent, yet cachexia developed rapidly. 

Case 5. 

A negro woman, aged 52, after a week of rather unusual feeble- 
ness, beginning about May 1st, went to bed from sheer weakness. 
She had been healthy and strong, did her own housework and 



28 PELLAGRA. 

washing, and weighed 172 pounds. At times everything seemed to 
swim before her eyes, and it seemed that her legs would give way 
under her when she stood or tried to walk. Her mouth was sore, 
her gums bled, tongue raw, and it even hurt her to swallow water. 
Diarrhea began and grew worse, and when she went to bed she 
noticed streaks of blood in the stools. Her hands and feet burned ; 
she had pains in the left back along the middorsal region; and on 
account of a constant feeling of nausea and this rawness in her 
throat she ate hardly anything. 

About May 10th she presented a characteristic roughness on the 
back of the fingers, hands, and extensor surfaces of forearms half 
way to elbows. On the back of the hands there were several 
blisters, varying in size from a pea to a quarter and containing 
serum, occasionally streaked with blood, with an ulcerated base. 
The dermatitis was symmetrical, and one could not help thinking 
that the skin was similar to a burn. The roughness was not the 
usual color of the pellagrous erythema, but presented somewhat 
the appearance of an old negro's hand on a cold winter morning. 
It seemed at certain angles of a dark, ashy gray, and as if the dry 
skin would shed off in scales if the hands were well washed in 
warm water. There were patches of dermatitis on each side of the 
nape of the neck, and at the base of the alae of the nose. The 
ankles and shins were rough, and at times the feet and hands were 
slightly swollen. Her feet and hands burned severely at times. 

Temperature rose to 103.5°, with pulse at 120. Her eyes had a 
staring, vacant expression, and she looked wild and anxious. Re- 
flexes all exaggerated, and she lay in bed in a rather stuporous 
condition. Her mind rapidly failed her, and control was lost of 
the lower limbs. She seemed a mass of helplessness. Occasionally 
she grew rigid and half violent, and then relapsed into a stuporous 
condition. Her urine contained a trace of albumen, with a few 
hyalin and granular casts. Diarrhea continued until finally incon- 
tinence of urine and feces developed. Toward the close she de- 
veloped opisthotonos, though most of the time she was rather quiet 
and rigid. She died on June 6th, with a temperature of 105, but 
the fever ranged from 101 to 104 after she went to bed. After 
death she looked as though she had lost forty or fifty pounds. The 
rapidity of the disease, its increasing severity until death, gave one 
the impression that the patient was suffering with an acute infec- 
tious disease. Diarrhea, temperature, high pulse, prostration, 
emaciation added evidence confirming this idea. 



GENERAL CONSIDERATIONS. 29 

Discussion of Case 5. 

This is typhoid pellagra, or the tifo pellagroso of the Italians. 
The eruption was a wet dermatitis, and the attack grew rapidly 
worse. Notice the tendency to muscular rigidity and opisthotonos. 
The kidneys were involved. Stomatitis and anorexia severe. The 
continued fever distinguished this form. Death in five weeks. 

DEFINITION. 

Pellagra is an endemic and epidemic disease, periodic and 
progressive in its course, and characterized by a series of symptoms 
involving chiefly the digestive, cutaneous, and nervous systems. 

GENERAL DESCRIPTION. 

Pellagra may be endemic in country communities for a century, 
as in Italy, or suddenly epidemic, as in America. It varies in 
length from the six weeks' course of typhoid pellagra to twenty 
or thirty years, or even longer, of the chronic forms. It finds its 
chief home in the country districts, and attacks all classes, all 
ages, and both sexes, but does not attack dwellers in crowded 
cities. The attack begins usually in the spring and summer 
months, recurring with increasing severity every spring. A sec- 
ond attack may occur in the late summer or autumn months, with 
remission of symptoms and improvement during the winter. Its 
onset is insidious, its attack is periodic, and its course is progressive. 
The symptoms of the digestive tract are stomatitis, esophageal 
burning, pyrosis, gastralgia, belching, nausea, gastritis, enteritis, 
dyspepsia, diarrhea usually and constipation rarely. The chief 
cutaneous symptoms are a peculiar, bilaterally symmetrical ery- 
thema, with progressive desquamation and pigmentation, a branny 
roughness of symmetrical skin areas, occasional serous or bloody 
blisters, and trophic changes around the nails. The chief nerve 
symptoms are a chronic neurasthenia, exaggerated reflexes, vertigo, 
ataxia, spastic and paralytic gaits, palsies, and paralytic strokes; 
occasional ankle clonus and Babinski reflex. Mental symptoms 
include sadness, melancholia, dementia, mania, confusional insanity, 
mutism, murder, and suicide. Emaciation and chronicity go hand- 
in hand. The diagnosis is generally easy, and the prognosis varies 



30 PELLAGRA. 

with, the type of the disease and the time treatment is begun. An 
early diagnosis is important. 

IS PELLAGRA CONTAGIOUS? 

Endemic and epidemic diseases spread by contagion or the con- 
veyance of a disease from one person to another by direct contact, 
as illustrated by small-pox; by bacterial infection of one person 
by germs from another, as illustrated by the tubercular infection 
of a wife from a tubercular husband; by bacterial or protozoan 
infection through the bite of an insect which acts as host, as illus- 
trated by malaria and yellow fever by different mosquitoes; by 
bacterial or parasitic infection through food and water, as illus- 
trated by cholera and trichina spiralis; by parasites burrowing 
through the skin, as illustrated by scabies and uncinariasis. As 
the cause of one disease after another is discovered, the number 
of diseases officially classified and popularly called "contagious" 
continues to decrease. Yellow fever a short time ago was always 
and everywhere considered contagious, and a medical man who 
would have disputed the contagiousness of yellow fever would have 
been considered foolish indeed, yet yellow fever is not at all con- 
tagious and the criminal is a mosquito. 

Applying this classification to the transmission of pellagra, two 
facts are clearly apparent — (1) pellagra is not transmissible by 
contagion from one person to another; (2) pellagra is not trans- 
missible by infection from one person to another. It is neither 
contagious from person to person, as smallpox, or infectious from 
person to person, as tuberculosis. In certain quarters there is ob- 
jection to the use of the word contagious, but, until the real cause 
of every disease is discovered, this word is needed. The truth, of 
these two propositions denying the transmissibility of pellagra is 
amply proved by the following facts: 

1. The limitation of pellagra to the rural population. People 
who live in cities need have no fear of the disease, because pellagra 
stops at the city gates. Paved streets, high buildings, and crowded 
populations are not its home. This is one of the outstanding facts 
of the disease. Because pellagra develops in villages and towns 
of a few hundred or a few thousand inhabitants does not contradict 
the immunity of cities. Especially in the southern states these 
villages are under the same condition of living and environment 



GENERAL CONSIDERATIONS. 31 

as far out in the country. An investigation of many of these 
so-called city cases will reveal the fact that they contracted the--- 
disease in the country, or spent much of their time in rural dis- 
tricts. 

2. The limitation of the disease in many cases to large families 
or to several families living together under the same conditions of 
daily life. Alessandrini found 269 Italian families of 1,659 per- 
sons, and only 274 pellagrins among them, and of these only five 
families had 2 pellagrins each. One family of 21 members and 
another of 13 had only one pellagrin in each. 

3. The complete immunity of hospitals, asylums, orphan homes, 
hotels, summer resorts, and all institutions where pellagrins are 
admitted for temporary or permanent residence. Nurses and at- 
tendants who stay with pellagrins all the time, physicians who 
treat them, relatives who live and sleep with them, are all alike 
immune. At the pellagrosari in Inzago, Mogliano Veneto, and 
Rovereto, where thousands of cases have been treated, no physician, 
nurse, or attendant has ever developed the disease. 

4. The enormous intercommunication between urban and rural 
populations, and the absolute failure in any instance of pellagra 
to develop along the highways and lines of travel, or in cities where 
exposure in pellagra countries is constant. 

5. It is impossible to reproduce the disease by inoculation from 
the serum exuded from the skin or from the blood and saliva 
of pellagrins. It is impossible to convey the disease from pel- 
lagrous wet-nurses to suckling infants in lactation. Here the very 
food of the infant is secreted from the blood of a pellagrin, and yet 
there is no record of the transmission of the disease to the infant. 
Sambon quotes Nardi in a conclusive way: "Although several 
children belonging to the upper classes of this town (Milan) were 
suckled by women recognized to be pellagrins at the end of lactation, 
nevertheless, notwithstanding that some of 'the nurslings have now 
passed their fifteenth year of age, not one of them exhibits any 
sign of having contracted the nurse 's disease. ' ' I know of no better 
way to test the contagiousness of the disease than this, and espe- 
cially since these cases were observed for a period of fifteen years. 
It is a common observation in medicine that nursing infants are 
easily affected by a disease or even passing illness of the mother, 
and the susceptibility of infants to contagious diseases is well 
known. The contagiousness decreases with age, as illustrated by 



32 PELLAGRA. 

scarlet fever and mumps, and, if there is a remote possibility of 
contagion in pellagra, it should appear in infants nursing pella- 
grous milk, and the development of the disease would not be long 
delayed. It did not develop in such nurslings either during in- 
fancy or thereafter. 

6. In the surgical procedure required for the transfusion of blood 
from a healthy donor into a pellagrin in the last stages of the 
disease, open wounds in both are brought in contact, vessel is joined 
to vessel, and for periods exceeding an hour. The disease is at 
its height, and, if either contagion or infection were possible, it 
would be at this time, and yet there has been no development of 
pellagra in any donor. 

In the country districts in Italy and in America there is unques- 
tionably an uncertainty of belief regarding contagion, and a suspi- 
cion in areas where, the disease develops with great rapidity that 
it is somehow contagious. In an area of less than one-half mile 
in length along the banks of a small branch and pond near Forsyth, 
Monroe county, Georgia, 5 cases of pellagra originated. Elrod, 
of Forsyth, who drove me out to this endemic area, called my atten- 
tion to the fact that there were no cases between these and the 
town of Forsyth, nine miles away, and how easy it would be to 
believe in the contagiousness of the disease if one merely viewed 
these 5 cases. It is easy in the popular mind to believe that, if a 
disease spreads in a community, it is therefore contagious, but the 
medical mind knows how false is this assumption. Pellagra does 
spread in one of its endemic areas, not because it is contagious, 
but because the people live in this area under the same conditions 
and are subject to the same causes of the disease. The point is that 
a pellagrin can not convey the disease by removing to a nonendemic 
area, but a well person can contract the disease by moving into an 
endemic area. 

It is important that this matter be understood, and the fears of 
relatives and friends of pellagrins be allayed. I have known a 
young lady to develop the disease, her friends to forsake her, and 
her relatives to appear only when necessary and in plain fear of 
the patient lest they contract the disease from her. Pellagra is 
bad enough, and the sadness symptomatic of the disease is sufficient, 
without causing the pellagrin to feel that she is a menace and a 
source of contagion. It would be different if it were true, but 
pellagra is not contagious. 



GENERAL CONSIDERATIONS. 33 

WHICH SEX IS MORE AFFECTED? 

More women than men suffer with pellagra. This is one of the 
striking features of the disease. A study of groups of cases re- 
ported by general practitioners in America reveals the constant 
preponderance of female pellagrins. A few of these taken at 
random follow : 

Seven cases, 5 women and 2 men ; 24 cases, 14 women and 10 men ; 
9 cases, 8 women and 1 man; 10 cases, 7 women and 3 men; 18 
cases, 13 women and 5 men ; or of these five groups, with a total of 
68 cases, 49 were women and 19 men. The following groups from 
the American asylums for the insane report somewhat the same 
proportion : of Zeller 's 130 cases from Illinois, 75 were women and 
55 men; the Cook county institutions in the same state report 26 
cases, with 13 of each sex; the East Mississippi Asylum reports 
9 cases, 7 women and 2 men; in the Florida Hospital for the In- 
sane, among 85 women there were 11 pellagrins, and among 240 men 
only 2 pellagrins. Along the foothills of the Alps in Umbria, Italy, 
Alessandrini found in one area 254 pellagrins, 192 women and 62 
men. In Roumania, of 19,796 cases 9,132 were men and 10,664 
were women. 

Warnock's report from the Egyptian government hospital for 
the insane for the nine years from 1901 to 1909 inclusive gives 636 
pellagrous admissions, and of these 477 were men with 69 deaths, 
and 159 were women with 24 deaths. The figures of both Sand- 
with and Warnock seem to prove that in Egypt at least there are 
more men than women affected, but their figures are from hospital 
and asylum sources. In Italy, in 1847, out of 1,503 pellagrins in 
Venice and Piedmont, 658 were men and 854 women, a proportion 
of 4 to 5 ; another group of Italian statistics gives 2,289 men and 
2,478 women. Dr. Fritz, at Inzago, in the province of Milan, 
after an experience of thirty years with the disease believes women 
always suffer more than men. The proportion of male to female 
cases in the United States is from 1 to 4 to 3 to 4, depending on 
the locality ; the average is probably about 2 to 4, as illustrated by 
Porter's Florida figures of 33 men and 41 women. Grimm found 
111 females and 29 males in three Kentucky counties ; and of 189 
deaths from pellagra in Texas, 153 were females and 36 males. 

Nowhere have I found any adequate explanation of the excess 
of pellagra in women. In Italy it is said that more women have 



34 



PELLAGRA. 



pellagra because they work in the fields, but more men than women 
work in the fields in Italy and for longer periods. Sandwith's 
Egyptian cases show more men, and he thinks that it is because the 
women are not field laborers to the extent that they are in Italy. 
In America the women, as a rule, are not field laborers, and prob- 
ably the vast majority of women pellagrins in this country never 
work in the fields. Some of them pick cotton in the fall for a 
very short time in the South, but this hardly accounts for the 
cause. In Italy and the southern states one may see large num- 




Fig. 2. — Dermatitis on hands of pellagrin. Skin dry, with exfoliation. 

(After Merk.) 



Note the wrinkles. 



bers of women doing the washing for the family in some sheltered 
swamp cove where a spring arises or beside some running stream. 
This work takes the women outdoors far more in America than 
any farm work. Furthermore, men are far greater consumers of 
corn products than women. It is certain that the prevalence of the 
disease among females can not be attributed to the additional 
burden of childbearing. It is as natural for women to bear chil- 
dren as for men to work, and, what is more important, the same 
preponderance of females holds in comparing pellagrins of both 
sexes under 18 years. Women are neither more predisposed nor 



GENERAL CONSIDERATIONS. 35 

less resistant to pellagra than men, and we must look to a greater 
exposure of women to the active cause of pellagra to account for 
the greater number of female pellagrins. This matter is discussed, 
further in Etiology, page 263. 

IS PELLAGRA INHERITED? 

One of the questions asked of the physician, and one he often 
asks himself, is whether pellagra is inherited. Heredity is too 
vast a problem to be dismissed with a "yes" or "no" until one 
knows exactly in what way the word heredity is used. The under- 
standing of the heredity of diseases is not as easy as counting chro- 
mosomes or comparing colors in the offspring of animals. There 
are as many opinions on the question as there are writers on the 
subject, and the answer has depended largely on the opinion of 
the writer. 

Another unconscious influence has held sway — more, perhaps, 
than has been realized. This relates to the theory one accepts as 
to the cause of the disease. It is obvious that if one accepts the 
corn theory, and believes the disease due to toxins acting in the same 
individual for a number of years, it is very easy for him to believe 
that the same toxin can easily ensconce itself in some organic way 
in the ovum, reappear in the child, and continue to poison the 
infant. If one accepts the parasitic theory of the disease, he must 
either refuse to believe in its heredity or else postulate a new theory 
based on the idea that the cause is a germ or parasite with which 
the embryo becomes infected. One asks, if a toxin continues to 
act for ten years in the body or somatoplasm, why may it not con- 
tinue to act through the germ plasm ; the other refuses to believe 
the disease inheritable, or believes the embryo may become infected 
Avith the unknown organism. 

Viewed from the accepted idea of modern medicine, a disease 
is inherited when the child has the disease at birth, as when a 
syphilitic child is born of syphilitic parents. It begs the question 
to say that syphilis is not inherited because the embryo was in- 
fected by the spirocheta pallida during gestation. One or both 
parents had syphilis, and their child at birth had the disease, illus- 
trating the direct transmission of disease from parent to offspring. 
In the sense, then, that the germs or parasites may be contained 
either in the ovum or spermatozoon, or that the toxins may affect 



36 



PELLAGRA. 



these, or may through the fetal circulation and the placenta cause 
the disease to be present in the child at birth, one may say that pel- 
lagra is distinctly not inherited. As Sambon well says, there is no 
record of a child born with the characteristic signs of the disease 
upon it. Children are born with syphilis, but children are not 
born with pellagra. The disease pellagra in one or both parents 
does not reappear as the disease pellagra in the newborn infant. 
Even Lombroso, who believed firmly in the heredity of pellagra, 
did not believe the disease appeared in the offspring before the 
second year, and then not as pellagra, but as pellagra without the 




"Fig. 3. — Dermatitis on feet of pellagrin. Skin peeling, with edema on left foot. (After 

Merk.) 

eruption — pellagra sine pellagra — but we shall see that he mistook 
the degeneracy caused by pellagra for hereditary pellagra. At 
this point has originated the difference of opinion and the various 
beliefs regarding its heredity. 

Pellagra is too recent in America to permit any statistics on 
heredity, but the family reported by Watson had three children, 
all pellagrins; both parents healthy, all living under the same 
conditions, and yet only the children developed the disease. Here 
healthy children developed pellagra, but, had they been born with 
a congenital weakness of any organ or feebleness of the entire sys- 
tem, it is reasonable to believe they would have developed pellagra 



GENERAL CONSIDERATIONS. 37 

or any other disease very much more easily. A pellagrous parent 
is not a healthy ancestor, and predisposes his offspring to the attack 
of any widely prevalent disease. 

Heredity depends on the quality of the sperm, the quality of the 
germ, and their suitability to each other. Gross errors in either 
parent tend to reappear in some form in the offspring, and par- 
ticularly is this true of neurotic errors in the parent. An epileptic 
or a hard drinker is not apt to produce a child without some 
flagrant neurosis or mental weakness. The pellagrin suffers not 
only a chronic neurasthenia, an ever increasing tendency to 
melancholia, but also actual organic changes in the cord and brain. 
These organic changes do not appear in the child, but the stigmata 
of degeneracy do appear. Pellagra is not inherited, but the result 
of its ravages in the parent is inherited, and appear in the child 
in the form of dwarfism, deficient development, anemia, various 
malformations of the skull, asymmetry, bad set ears, mental weak- 
ness, slow growth, an unusual lack of resistance, and a frailness 
out of all proportion to age. In addition to pellagra, the parent 
may also have ankjdostomiasis, or be tubercular, syphilitic, or 
alcoholic, and the degeneracy in the child would thus be increased. 
Let this continue for two or three generations, and it is natural to 
find the descendants of pellagrins suffering with the widely preva- 
lent disease of the community, and increasingly degenerate and 
pauperized. Pellagra thus becomes a real cause of race degeneracy. 
These children live under the very same conditions in which their 
parents developed pellagra, and their very degeneracy is, in turn, an 
invitation to the disease already widely prevalent. If strong men 
develop pellagra, frail children will develop pellagra much more 
easily. The injurious influences are at work, and both parents and 
children may be attacked at the same time, or children may become 
pellagrous first and their parents afterward. The excellent table 
on page 38 prepared by Boudin is worthy of study. 

The first three groups, with pellagrous parents, give 443 
pellagrous children, while the last two groups, with parents well, 
give 297 pellagrous children, an excess in favor of pellagrous 
degeneracy and predisposition of only 20 percent. Even this is 
enough to furnish evidence that adult pellagrins should not marry 
and add a burden to the race in the form of degenerate children. 
Dr. Fritz, at Inzago, in the province of Milan, told me that he had 
noticed that pellagrous children, attacked in early childhood and 



38 



PELLAGRA. 



recovering rapidly, often married and had healthy families, with 
no pellagrous children. The disease in them did not pass the ini- 
tial stage or become confirmed, and they were healthy men and 
women when they married. 

Parents. Number Pellagrous children. Total 

married couples. Boys. Girls. children. 

Father and mother 96 116 146 262 

Father pellagrous, mother 
well 160 64 49 113 

Mother pellagrous, father 

well 175 30 38 68 

Father and mother well, 
two or more children pel- 
lagrous 43 59 53 112 

Father and mother well, only 

one child pellagrous 185 80 105 185 

1. Pellagra, as such, is not inherited. 

2. The children of pellagrins are apt to be of inferior physique 
and have stigmata of psychophysical degeneracy. 

3. Pellagra is thus a cause of race degeneracy. 

4. Adult pellagrins should not marry. 



AGE. 

Pellagra may occur at any age. The youngest cases I have 
found were in infants of 4 and 5 months, and the oldest in a man of 
99 and a woman of 102. Casal, Strambio, and Sambon report cases 
in octogenarians, and Siler found a case of 85 in Illinois, the oldest 
reported American case. In Egypt, Sandwith did not see any 
cases under 5, they were rare under 10, and most of the cases 
occurred in men in the prime of life. He considers puberty in 
boys a vulnerable time for the pellagrous attack. Sambon found 
in the country districts of Italy one family of eleven members, the 
youngest an infant of 16 months, all pellagrins; and a family of 
seven, the father aged 44, all pellagrins except the 4 months' old 
baby. Cases in children from 2y 2 to 10 years of age are found in 
the United States, but pellagra in infants is certainly not as com- 
mon as in Italy, or, if so, it is either overlooked or not reported. 
It is probable that, as the disease is studied in greater detail in the 
country districts, more cases will be discovered in children. Often 
in the little ones the erythema is so slight and transient, the other 



GENERAL CONSIDERATIONS. 39 

symptoms not at all severe, that the disease passes unsuspected and 
unnoticed. This is certainly the case in Italy, and, in addition, the 
pellagrosari do' not take the younger children and infants. 

The summary of different groups of statistics from different 
countries at different times permits a safe conclusion. Potarca 
collected 17,027 cases of pellagra, and found 13 percent under 20 
years, 31 percent between 20 and 40, and 56 percent over 40. 
Strambio gives 129 cases, with 15 percent under 25, 29 percent 
between 25 and 35, 67 percent between 36 and 60, and 3 percent 
over 60 years. Calderini studied 352 cases in 1844, and found 83 
of them under 3 years and 55 between 45 and 60. During the 
years 1905, 1906, and 1907 the pellagrosario at Rovereto, Austria, 
in the Tyrol, treated 456 cases, with an average age of 32% years. 
Of these 456 cases 275 were males, with an average age of 34% 
years, and 181 were females, with an average age of 29 years. I 
have collected 159 cases in the United States, reported chiefly 
from the country districts of the southern states, and it is inter- 
esting to note that the average age of these cases is 32% years, 
or the same as the 456 cases from Rovereto. This gives 615 cases 
from America and Italian Austria, with an average lower by 18% 
years than the 130 cases from Illinios, with an average of 51 
years, reported by Zeller. It is true that the average age of pel- 
lagrins in any state is lower than the average age of the insane 
pellagrins in the asylums of that same state; and, while most of 
the pellagrous area of the Union is not in the vital statistical area, 
we may assume with reason that the average age of pellagrins is 
in the fourth decade, and nearer 30 than 40. The Egyptian cases 
range around 40, while my own cases average 36 years. 

1. Pellagra may occur at any age, the average being about 35 
years. 

2. By far the larger number of pellagrins are between 20 and 40. 

3. Age influences neither the severity of the attack nor the course 
of the disease. 

IMMUNITY. 

The question of a natural immunity to pellagra is now merely 
a matter of observation, and can not be decided until experiment 
is substituted for observation, and then only after the cause of the 
disease is definitely known. Physicians and nurses are clearly 



40 PELLAGRA. 

immune to the disease from transmission by contagion. The ad- 
vocate of the corn theory believes all are immune as long as they 
do not eat corn, and the advocate of the parasitic theory believes 
in immunity as long as there is no infection with the parasite. 
The offspring of pellagrous parents is not immune, for he not only 
develops pellagra easily, but inherits a proclivity to disease in 
general. The inhabitants of an area where pellagra is endemic 
are not immune, because pellagra is there all the time, and individ- 
uals of their strength and environment constantly develop the 
disease. Furthermore, it is difficult to believe that a disease which 
admittedly is unable to confer acquired immunity is to any degree 
able to permit a natural immunity. Natural immunity is probably 
always only another name for variation in susceptibility. In- 
dividuals vary in susceptibility to pellagra as they vary in other 
diseases, and probably to a greater degree, as evidenced by the 
rapidly fatal and slowly chronic forms, the failure of certain in- 
dividuals to develop the disease when living in the same environ- 
ment, eating the same food, doing the same work, and exposed to 
the same influences as their brothers and sisters who become 
pellagrous. An individual may develop pellagra and be cured, or 
he may have pellagra with a recurrence ten years later. In this 
latter case there was either a reinfection or a reintoxication after 
a period of protection conferred by the first attack — a kind of 
pellagrous vaccination — or the parasites were latent this long 
period. A latent intoxication for twelve years is to me unthinkable. 
Parasitic infection permits and rather predisposes to reinfection, 
especially when the environment continues the same. There is 
probably neither a natural nor an acquired immunity to pellagra, 
but there is probably a variation in susceptibility to the disease, and 
certainly a variation in exposure to the causative agent. For in- 
stance, even when pellagra is epidemic, the crowded city escapes 
the disease, as illustrated by Milan, in Lombardy, in the last 
century. Even in country districts one area may be pellagrous, 
and another near by free from the disease, and this condition con- 
tinue for long periods of time. 

OCCUPATION. 

At the Ospitale Maggiore, in Milan, pellagra is classified as a 
disease peculiar to farmers and peasants, just as lead poisoning is 



GENERAL CONSIDERATIONS. 41 

confined to workers in lead. The triple cause of pellagra in the 
popular mind included this idea as expressed in the axiomatic 
phrase, ' ' Peasant life, poverty, and polenta. ' ' That peasants, field 
workers, and farmers are peculiarly susceptible to pellagra is the 
opinion of writers in Spain, Italy, Egypt, and Roumania. Our 
experience so far in America does not agree with this altogether, 
and a study of Sambon's Italian report shows facts more nearly 
similar to conditions in America. 

J. C. Johnson, of Atlanta, reports 20 cases of pellagra, with 
the following occupations : farmers, 2 ; merchants, 3 ; lawyers, 1 ; 
minister, 1 ; teacher, 1 ; salesman, 1 ; housewives, 10. From this 
series of 20 cases it will be seen that there are only two who worked 
in the fields, and that three of the four professions are repre- 
sented. Consulting articles by different authors who report Amer- 
ican cases, I find one group of 5 cases, all living in the country, 
but no farmers or field workers among them; another of 8 cases 
with only one farmer; of 6 cases one was a farmer and all lived 
in the country; of 10 cases 1 was a farmer, 1 a lawyer, 1 a car- 
penter, and the others housewives. It is probably true that a 
majority of the adult white pellagrins in America do not work 
in the fields, nor have I been able to find any record of pellagrous 
children who did farm work to any extent. What is of vastly 
more importance is the fact that practically all the pellagrins in 
America either live in the country districts, or in villages where 
the conditions and environments are the same as in the country. 
Procopiu says that pellagra exerts a preference for farmers, but 
it would be more correct to say that it exerts a preference for 
those who live in the country or in a rural environment, and this 
without reference to occupation. Environment, rather than occu- 
pation, is the predisposing and determining factor. 

When I told Dr. Bezzola, of Milan, that pellagra occurred among 
the well-fed and highly nourished individuals in the South as well 
as among the poor, he expressed his astonishment and said that 
he even doubted that the disease was pellagra, so firmly was the 
idea of farmer and poverty as the united host of pellagra fixed in 
his mind. The physicians in the country districts of the southern 
states bear witness to the excess of female pellagrins and the rarity 
with which they work in the fields. Sambon found pellagra in 
coachmen, fishermen, priests, shepherds, carpenters, masons, in a 
shoemaker, and found in one case a hesitancy on the part of some 



42 PELLAGRA. 

physicians to diagnose pellagra because the pellagrin was a cul- 
tured lawyer. He found in Italy, as is true in America, that 
members of the wealthiest families have the disease, but all these 
were rural in their habitations and lives. Of 1,955 deaths from 
pellagra in Lombardy from 1848 to 1859, the number of country 
people was 1,853 ; all the 150 lunatics in the asylum at Modena 
were from the country; of 148 insane pellagrins only 9 were not 
peasants, and even these were mostly born of pellagrous parents. 
About the same proportion holds in Corfu and in Roumania. 
Sandwith found of 137 cases 88 percent were peasants, 6 mason's 
laborers, 4 beggars, 3 boatmen, 2 policemen, 2 brickmakers, 1 potter, 
1 servant. 

I have seen three physicians in Georgia who stated that mem- 
bers of their families were pellagrous. They were cultured and 
refined men, and their families were in good circumstances. One 
mayor of a Georgia village developed the disease and died in a 
short time. 

Pellagra is not limited to, nor does it exert a preference for, 
those engaged in any one occupation. Taking the pellagrous area 
of the world, it is probable that more farmers will have the disease 
than those of any other occupation — not because they are farmers, 
but because pellagra is limited to country districts, and a majority 
of the rural inhabitants are farmers. Probably a majority of 
American pellagrins do not work in the fields, but practically all 
American pellagrins live in a rural area. 






CHAPTER II. 

HISTORY AND GEOGRAPHICAL DISTRIBUTION. 

In nearly every country in which, pellagra has developed, the 
disease was known among the people in the rural districts before 
it was known in the medical literature of the country. The name 
pellagra itself was given the disease by the common people and 
not by a physician. 

There are about sixty synonyms, which include names given by 
the people in Spain, Italy, France, Austria, Egypt, and America 
to the symptom complex known in medicine today as pellagra. 
Some of these are interesting in that they embody the double idea 
of symptom and of cause — as, for instance, scottatura de sol (the 
burning of the sun), which refers, of course, to the dermatitis and 
to the fact that the sun was at one time considered the cause of 
pellagra. Another idea conveyed by some of these synonyms is 
that pellagra at first was not considered as a separate disease, but 
a condition comparable to erysipelas, to scurvy, and to leprosy. 

Among the synonyms that originated in Spain are : 

Spanish Synonyms. 

Mai de la rosa — sickness of the rose. 

Mai de Asturias — the disease of the Asturias. This refers to 
the ancient province of Asturia in Spain, where the disease first 
originated. According to the redivision of Spain in 1833, this 
province took the name of Oviedo. 

Mai del higado — disease of madness. 

La gala de Saint Agnant, or sometimes written La gala de Saint 
Ignace — the itch of Saint Ignace. 

Calor del hidago — burning of the person. 

Escamadura del hidago — a desquamation of the person. 

Flema salada — the salty phlegm. This refers to the salty taste 
occasionally persisting in pellagrins. 

43 



44 PELLAGRA. 

French Synonyms. 

Mai du maitre — the master's disease. 

Maladie de la Teste — the disease of Testa, Gironde, France. Pel- 
lagra originated in France in the vicinity of Teste. 

Eruption de Lombardie — the Lombardian eruption. Pellagra 
originated in Italy in the province of Lombardia. 

Mai de saintes mains — the sickness of the main saints. 

Mai de Sainte Eose — sickness of Saint Rose. 

Mauvais dartre — a bad eruption. 

Italian Synonyms. 

Mai della spienza — disease of melancholia. , 

Mai del monte — disease of the mountains. 

Mai del padrone — the master's disease. 

Mai del sole — the disease of the sun. 

Scottatura de sole — the burning of the sun. 

Jettatura di sole — the evil eye of the sun. 

Umor salso — the salty humor. 

Mai salso — the salty disease. These last two refer to the salty 
taste present in the mouth of some pellagrins. 

Cattivo male — the wretched disease. 

Mai della vipara — the disease of the viper. 

Psychoneurosis maidica — the psychoneurosis caused by corn. 

Pelandria, pellarela, and pellarina are dialectic corruptions of 
the ordinary pellagra. The first is used in the rural districts 
of Pavia. 

Mai roxo, mal rosso — a blushing disease. 

Pellis aegra — the rough skin. 

Risipola Lombardia — Lombardian erysipelas. 

Lepra Italica — Italian leprosy. 

Maidica — the corn disease. 

Malattia della miseria — the disease of the poor. 

Raphania maistica — the corn shapping. 

Malattia del insolata di primavera — disease of the sun's rays in 
the spring. 

Calore del fegato — the heat of madness, 
' Salso — salty, biting. 

Scorbuto mantano — mountain scurvy. 

Scorbuto Alpino — Alpine scurvy. 






HISTORY AND GEOGRAPHICAL DISTRIBUTION. 45 

Lepra Asturiensis — Asturian leprosy. 

Elephantiasis Italica — Italian elephantiasis. Referring to the 
skin in the third stage. 

Greek Synonym. 

Graeci elephantiasim — Grecian elephantiasis. 

Roumanian Synonyms. 

Buba tranjilor — refers to the pimples of the dermatitis on the 
back of the hand. 

Rana tranjilor — refers to the roughness Avith the skin divided 
up with a supposed similarity to a frog's skin. 

Parleala — a burning. 

Jupuiala — a desquamation. 

German Synonym. 

Der Lombardische aussatz — Lombardian leprosy. 

Egyptian Synonyms. 

Inshuf — chapping. 

Gofar — an eruption in camels and sometimes horses, and given 
by the fellaheen to the dermatitis in pellagra. 

Among the synonyms which have become current in the English 
language are scorbutic paralysis, land scurvy, and Italic scurvy. 
An interesting fact is the origin of synonyms in the United States. 
Three are in common use among the people in the southern states, 
where pellagra is known as "the corn bread disease," "corn bread 
consumption," and "corn bread fever." 

A study of these synonyms is very interesting, as it brings out 
some of the early ideas current concerning the disease. Mixed 
with these, of course, is an element of fact. Several of the syno- 
nyms refer to the sun, because in the early days the sun was 
believed to be the cause, and even now the part played by direct 
sunlight in the eruption is not clearly understood. Several refer 
to the mountains, making evident the fact, as is well known, that 
pellagra is found chiefly in a rolling country toward the foothills 
of the mountains as well as up in the mountains themselves, where 
the streams have cut deep and narrow valleys among the hills. 

There are several references to the salty taste in pellagra and 
to the fact that pellagra is a disease of the poor. The word scurvy 



46 PELLAGRA. 

as regards pellagra occurs because in the early days in Italy pel- 
lagra was considered a form of scurvy. . 

Different words relating to heat and burning are, of course, ap- 
plied because of the sensations of burning often present in the 
hands and feet. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 

The history of pellagra resolves itself into the history of the 
disease and its distribution in the several countries where it has 
appeared during the last two centuries. Pellagra may be said to 
have had six epochs, beginning probably about 1700 in Spain and 
extending to the present time in the United States of America. 
These six epochs may be called (1) the Spanish epoch, dealing 
with pellagra in Spain; (2) Italian epoch, dealing with pellagra 
in Italy; (3) French epoch, dealing with pellagra in France; (4) 
Austria-Hungarian epoch, dealing chiefly with pellagra in Austro- 
Hungary, Turkey, Boumania, and Greece; (5) Egyptian epoch, 
dealing with pellagra chiefly in Egypt and to a lesser extent in 
other parts of Africa; (6) American epoch, dealing with pellagra 
in North and South America, but chiefly in the United States. 
These epochs will be taken in order, and the history and distri- 
bution of the disease in each country discussed. 

Spanish Epoch. 

Pellagra originated in the northern part of Spain on either side 
of the Cantabrian range of mountains, which form that part of 
Spain known originally as the Asturias, but which is now on the 
northern side of the mountains the province of Oviedo and on the 
southern side the province of Leon. Casal wrote in 1735 in the 
city of Oviedo a treatise which he called the "Natural History of 
the Asturias," and in which what we know today as pellagra was 
called mal de la rosa — the sickness of the rose. His book was 
written in Latin, and it is interesting to know that this book has 
been translated into Spanish and printed in Spain in 1900. I 
found a copy of it in the British Museum. Thiery, a French 
physician, was familiar with the contents of Casal's treatise, and 
wrote a description of the mal de la rosa in the Journal of Medi- 
cine of France, 1755, II, 557. Casal's book was not really pub- 
lished until 1762. 






HISTORY AND GEOGRAPHICAL DISTRIBUTION. 47 

Townsend, an Englishman, in his "Travels Through Spain" (vol. 
I, page 289, published in 1787), in writing of a visit which he made 
to the hospital at Oviedo, the capital of the Asturias, refers to 
this mal de la rosa, the first reference to the disease I have been 
able to find in the English language. Of this hospital he says : 
1 'The most remarkable cases were tertians, dropsies, and a disease 
peculiar to this province called mal de la rosa. This disease is 
considered a species of leprosy, and descends the sternum nearly 
to the cartilago xiphoides. Those who suffer with this disease have 
a peculiar propensity to drown themselves. "When the disease is 
neglected, it terminates in scrofula, marasma, melancholy, and 
madness. The people among whom it originates eat little flesh in 
their food ; they drink little wine. Their usual diet is Indian corn, 
with beans, peas, chestnuts, apples, pears, melons, cucumbers; and 
even their bread made of Indian corn has neither barm nor leaven, 
but it is unfermented and in a state of dough. Their drink is 
water. ' ' 

From the province of Oviedo pellagra spread westward into 
northern Portugal and south into the provinces of Leon, lower 
Aragon, and Burgos. The second focus of pellagra in Spain 
seems to have been in the province of Guadalajara, just west of 
Madrid and in the midst of the Sierra de Guadarrama mountains. 
The third focus was in southern Spain in the province of Granada, 
in the midst of the many ranges of mountains in southern Spain. 

The Academy of Medicine in Barcelona in 1879 made an inves- 
tigation of the prevalence of pellagra in Spain, and, with certain 
limitations, according to Hirsch, the following facts may be ac- 
cepted: The Asturias were the chief center of the disease at that 
time, and to a lesser degree lower Aragon and Burgos. In fifty 
villages in the province of Guadalajara 2 percent of the popula- 
tion were affected. The other provinces chiefly affected at that 
time were Cuenca, Navarra, Zaragoza, Zamora, and Galicia. A 
few cases were found in all the other provinces in Spain. Since 
that time the number of cases has decreased and the severity of the 
disease has greatly lessened. From a report of the Fourteenth Inter- 
national Medical Congress, held in Madrid in 1903, it appears that 
only twenty cases were observed in the Asturian districts where 
the disease first became known. There has been a marked decrease 
in the number of cases since 1900. Nearly all of the twenty cases 
above mentioned terminated by death of the infected person, largely 



48 PELLAGRA. 

on account of lesions of the spinal cord. It is stated that the 
rapid decrease of the pellagra has been due to the general im- 
provement in hygiene, food, and cleanliness among the laboring 
classes. For these facts concerning the present history of the dis- 
ease I am indebted to Consul General Morgan, of Barcelona, Spain. 
There are probably more cases in the province of Madrid than in 
Oviedo at the present time. 

Spain, topographically, is a rolling, mountainous country, con- 
sisting of hills, narrow mountain valleys, and swift-running 
streams. In those portions poorly watered a system of irrigation 
is used which dates from the Roman and Moorish periods. The 
chief cereals in order are wheat and barley, oats and rye. Corn 
is cultivated in all the provinces, but not to a great degree. Indian 
corn began to be used in Spain probably in the sixteenth century, 
and was doubtless brought there by the Spanish explorers from 
the West Indies and South America. The chief fact of impor- 
tance in the history of pellagra in Spain is that it nourished for 
nearly two centuries, and then for some reason since 1900 has 
ceased to exist to any great degree. 

Italian Epoch. 

Pellagra next appeared in northern Italy. Sambon has investi- 
gated at great length the time of this appearance, and from the 
evidence presented it was certainly prevalent there in the year 
1720. Dr. Bava said in 1781 that it has been known in the Ligurian 
mountains for over sixty years, and that it proceeded in the same 
order and manifested itself and grew with the same symptoms. 
Taraghi says the disease was noted before 1730 in the vicinity of 
Sesto Calende, on Lake Maggiore, just north of the present city 
of Milan. In these earlier days the oldest peasants said their an- 
cestors spoke of it as mal rosso and mal della rosa, according to 
Alvera quoted by Sambon. Frapolli was the first to use the word 
pellagra, a name which originated among the peasants themselves. 
It is altogether probable, considering the later history of the dis- 
ease and the fact that it has always seemed to have been present 
in a country a number of years before its discovery by the pro- 
fession, that pellagra existed in northern Italy as early as 1700. 
The history of pellagra since its appearance in Italy has been 
largely its history in that country. Despite the fact that it first 
appeared in Spain, more cases have appeared in Italy than any- 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 49 

where else in the world, and that country may rightfully be called 
the home of the disease. 

Pellagra has existed in forty-four out of the sixty-nine provinces 
in Italy. Dividing Italy into northern, central, and southern por- 
tions, the disease first appeared in the compartments of Piedmont, 
Lombardy, and Venetia, which form northern Italy. It then 
spread gradually southward, but always tended more to the east 
than to the west, and has always seemed to avoid the Genoan lit- 
toral. In addition to the three compartments already mentioned, 
it has nourished in Liguria and Emilia ; passing southward then 
into central Italy, it appeared in Tuscany, Marches, Umbria, and 
Latium, and to a small degree in Rome, Abruzzi, and Molise. It 
has avoided the southern compartments of Apulia, Campania, 
Basilicata, and Calabria. On the whole, however, pellagra has 
shown a constant tendency to extension southward. It has avoided 
the insular possession of Italy, and, strange to say, does not seem 
to have appeared in Corsica, Sardinia, and Sicily. 

The following tables show in table No. 1 the deaths from pellagra 
from 1898 to 1905 inclusive; table No. 2, the number of pellagrins 
in the entire kingdom of Italy as taken by four different censuses; 
and table No. 3, the number of pellagrins enumerated in the chief 
regions of Italy according to the last three censuses. 

Table No. 1 — Mortality. 

Years. Deaths from pellagra. 

1898 3,987 

1899 3,836 

1900 3,788 

1901 3,054 

1902 2,376 

1903 2,647 

1904 2,363 

1905 2,359 

Table No. 2 — Census of Pellagrins. 

First census ( 1879 ) 97,855 

Second census ( 1881 ) 104,067 

Third census ( 1899 ) 72,603 

Fourth census ( 1905 ) 55,029 

Notice the constant decrease since 1881. 



50 PELLAGRA. 

Table No. 3 — Pellagrins in the Different Nations by Census. 

Regions. 1881. 1889. 1905. 

Piedmont 1,328 1,223 1,012 

Liguria 56 30 56 

Lombardy 36,630 19,557 15,746 

Venetia 55,881 39,882 27,781 

Emilia 7,891 4,617 3,357 

Tuscany 924 1,125 1,137 

Marches 406 920 1,426 

Umbria 872 5,103 4,250 

Latium 32 146 195 

Abruzzi and Molise 

It will be noticed from these tables that the chief seats of pel- 
lagra have been Piedmont, Lombardy, Venetia, and Emilia. Pel- 
lagra seems to have originated in the district of Milan, then in 
Brescia, Bergamo, and Lodi, and then around Lake Como, Cre- 
mona, Mantua, and Pavia, so that by 1800 it covered practically 
all of Lombardy (Hirsch). In Venetia it appeared at Udine, far 
to the east of Milan and to the right of the Austrian Tyrol. In 
1787 the naturalist and poet Goethe, in his Italian journey from 
Verona, speaks of seeing patients with pellagra. In Piedmont and 
Liguria it has never developed to any considerable degree, and 
this is strangely true of Liguria. In Tuscany it appeared as early 
as 1785, but has not shown any marked increase in the last three 
censuses. Hirsch as early as 1885 stated: "Pellagra in Tuscany 
in more recent years has established endemic centers in the upper 
valley of the Arno, in Volterna around Lucca and Pisa, and among 
the hills near Florence. The disease appeared in Emilia about 
the same time that it appeared in Tuscany, though seven times 
more prevalent in the latter." In the last twenty -five years the 
disease has extended southward into the regions of Marches, Umbria, 
and Latium, and has been strikingly prevalent in Umbria. Now, 
according to Hirsch, as pellagra has extended into southern Italy, 
the cases in the earlier seats of the disease have increased — as, for 
instance, the history of pellagra in Lombardy shows that in 1839 
there were 20,282 pellagrins; in 1856, 38,777; and in 1879 there 
were 40,838 out of a total urban and rural population of 3,653,941, 
or 11.2 pellagrins per one thousand. In 1889 the cases show a 
decrease to 19,557, and a further decrease in 1905 to 15,746. 

The census of pellagra in Italy can not be relied on as more 
than approximately accurate. The total evidence, however, seems 
to show that at the present time there are about 50,000 pellagrins 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 51 

in the kingdom. The number of deaths per year shows a con- 
tinued decrease, so that there are probably less than 2,000 deaths 
per year from the disease, and that there are admitted into the 
asylums per year between 75 and 100 insane pellagrins. Certainly 
in Piedmont, Lombardy, and Venetia the disease is showing a rapid 
decrease, both in the number of cases and in the severity of the 
individual case. I found a good illustration of this fact at the 
Ospitale Maggiore in Milan. In former years several legacies were 
left to this hospital, the income from which was to be used in the 
treatment of pellagrins. The number of cases in the district of 
Milan and even in the adjacent country around the city had de- 
creased to such an extent that there were practically no cases and 
no demand for help. It is probable that in the course of the next 
twenty-five years pellagra in northern Italy will cease to exist to 
any extent. This is in harmony with the history and almost com- 
plete extinction of the disease in Spain. 

The Italian government, in view of the plague prevalency of the 
disease, has taken various measures in an attempt to stamp it out. 
These measures have all been based on the idea that the cause of 
pellagra is in some way connected with Indian corn. Therefore 
in Italy corn is the official cause of the disease, and various 
measures and institutions for the relief and treatment of pellagrins 
have thus originated. One of the most famous of these was the 
law of 1902, and, while this law has certainly not been well en- 
forced, there is a difference of opinion as to whether the decrease 
in the number of pellagrins has been due to what application this 
law has had or to other unknown causes. In Spain no preventive 
measures have been taken, and yet the disease has shown a greater 
decrease than in Italy. 

Sambon quotes Professor Sanarelli, under secretary of state for 
agriculture, in regard to this law and its results as follows : ' ' Not- 
withstanding the application of the law of July 21, 1902, for the 
prevention and cure of pellagra; notwithstanding the assiduous 
propagandism and the increasingly active endeavors of the pro- 
vincial pellagra commissions ; notwithstanding the great subsidies 
made by the state ; notwithstanding the locande sanitarie, the ex- 
change for bad maize, the dispensation of free salt, the encourage- 
ments given for the promotion of wheat cultivation, the teaching of 
sound agrarian principles, and many other direct or indirect meas- 
ures excogitated by private initiative and by the government to effi- 



52 PELLAGRA. 

ciently fight against pellagra, this disease in Italy does not show 
any tendency to decline in a satisfactory measure. 

"It is true that in these last years the general death rate from 
pellagra has gradually diminished, and that at first sight this 
marked improvement might appear to be due to the application 
of the law of 1902. But in comparing either the number of pel- 
lagrins or the number of deaths from pellagra in the three years 
1900-02 — that is to say, before the application of the law — with 
those of the three following years, 1903-06, one finds that all these 
figures do certainly indicate a gradual, progressive improvement, 
but an improvement which takes place in more or less the same 
proportions. A legitimate doubt, therefore, arises as to whether 
it be right to ascribe the gradual decline of pellagra throughout 
the kingdom to the measures contained in the law of 1902." 

The history of pellagra in Italy includes a reference to the 
measures used by the government to prevent the disease. Among 
these are the inspection of corn and the discovery and destruction 
of damaged grain. Some such measure as this was first authorized 
by the authorities in Venice in 1776. Efforts have been made to 
destroy damaged grain, but this law has been neither observed nor 
enforced. Practically all methods for the detection of damaged 
grain have failed. Sambon states that out of 44 Italian provinces 
affected by pellagra only 2, Venice and Padua, have a pellagro- 
logical inspector, whose duty it is to prevent the sale and con- 
sumption of damaged corn. Dr. Bresadola inspects corn at Ro- 
vereto, Austria. Efforts have been made to exchange sound corn 
for damaged corn, but this has been limited to one district in the 
province of Brescia. The royal law of 1884 tended to encourage 
the construction of plants for the drying of corn on the idea that 
corn spoiled and caused pellagra because it was gathered before 
it was dried. I have never been able to understand the necessity 
for these drying plants, because the Italian sun, like the Egyptian 
sun, is very warm, and what corn I had opportunity to examine 
in September and October was certainly dry and well seasoned. 
These drying apparatuses have never been used to any great ex- 
tent. For a short time in Milan and Coma rural bake-houses were 
established which aimed to be model bakeries, cooperative in plan, 
and to cook good, cheap, wholesome wheat and corn bread. They 
were not patronized and were not useful to any degree. 

Sporadic and spasmodic efforts have been made to abolish the 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 53 

late varieties of corn on the idea that corn reaching maturity in 
the autumn in forty to sixty days was immature and unhealthy. 
In regard to this it may be said that the second crop of corn in 
Italy is certainly not as large or as well developed as the first 
crop, but whether this second crop has anything to do with pel- 
lagra is a matter of serious doubt. In the Austrian Tyrol there 
is no second crop of corn, and yet nowhere on the earth has the 
disease been fiercer in type. The law of Italy requires what is 
known as the notification of cases, or, as understood in America, 
the law requires the physician to report cases of pellagra when 
first diagnosed, just as the law in the states requires contagious 
diseases to be reported. For many reasons, economical and in- 
tellectual, this report of new cases is neither accurate nor honest. 
Sambon (Progress Report, page 37) discusses this matter in full. 

Other measures include free meals to poor pellagrins for periods 
of not less than forty days twice every year. As Sambon wells 
states, this aims both to cure and prevent the disease, but the re- 
sults do not seem to bear out the statistics. By thus giving away 
food the law is imposed upon, and often the poor and ignorant 
who are not pellagrous are fed. In other cases these locande 
sanitarie are so far from the homes of the pellagrins that they 
are unable to reach them. The pellagrosario is an institution estab- 
lished as a pellagra hospital. Only those who are pellagrous are 
admitted, and they are lodged, fed, and treated at an expense borne 
jointly by the local province and the national government. The 
first pellagrosario was established at Legnano, in the province of 
Milan, in 1784 by authority of Joseph II. of Austria. For some 
reason it was discontinued after four years, but during that time 
the elder Strambio was physician in charge and here made his 
fame. At the present time the pellagrosari at Inzago, Citta di 
Castello, Mogliano, Veneto, and at Rovereto in the Austrian Tyrol 
are the most important. At all these the inmates are decreasing 
from year to year, and, as Dr. Bresadola remarked to me at Ro- 
vereto, ' ' soon the building will have to be used for other purposes, 
because there will be no more pellagrins." See page 65 for an 
illustration of the pellagrosario at Rovereto. 

French Epoch. 

Pellagra in France was first known through a report made by 
Hameau to the Society of Medicine in Bordeaux in 1828. He 



54 



PELLAGRA. 




HISTORY AND GEOGRAPHICAL DISTRIBUTION. 



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PELLAGRA. 




Tig. 5.< — Map showing distribution of pellagra in the United States. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 




Note predominance in the southern states — sporadic elsewhere. 



58 PELLAGRA. 

found the disease in La Teste de Buch, in the southwestern part 
of Gironde, a province of southwestern France bordering the Bay 
of Biscay. The disease was later found to have extended over 
the area known as the Landes, which lie to the south of Gironde. 
More cases developed in the latter than in the former department ; 
further south, in the valleys and hills of the Basses Pyrenees, in 
the department of Hautes-Pyrenees, and further eastward toward 
the Mediterranean in the Pyrenees Orientales. North of the 
Pyrenees around Toulouse and in the department of Aude endemic 
centers developed. Later, cases drifted into Paris, and sporadic 
cases, according to Hirsch, were found in the department of Seine- 
Oise, Marne, Allier, Maine-Loire, Ille-et-Vilaine, and Rouen. Pel- 
lagra existed in the regions south of Bordeaux from the time it 
was first observed by Hameau in 1818 for about fifty years, but 
since 1890 it has practically been an extinct disease, though during 
the last quarter of the last century a few cases w T ere admitted to 
the asylums for the insane. At the present time pellagra is not 
indicated in the French health statistics, and, if there are any 
isolated cases developing among the Pyrenees, they are either over- 
looked or not reported. 

The region in southwest France, where pellagra formerly flour- 
ished, is among the hills and valleys at the foot of the Pyrenees 
mountains. It extends then northward along the coastal plain; it 
is a country intersected and cut in all directions by flowing streams. 
The Landes was formerly a very unhealthy country, and the novel 
"Maitre Pierre" was written to show the unhealthiness of this 
region before it was drained. A French proverb refers to the 
ravages of pellagra in this area : 

"Taut que Lande sera Lande, 
La Pellagra te demande." 

"As long as the Landes are the Landes, 
Pellagra will demand you." 

The cause of the disease in this country was laid to many things, 
as air, water, food, millet seed, rye, maize, sardines, and salted eels. 
Corn is still cultivated in the Landes, the Basses Pyrenees, and 
adjacent departments in southwestern France. This area is just 
across the Pyrenees mountains from Spain and to the northeast 
of that country. 






HISTORY AND GEOGRAPHICAL DISTRIBUTION. 59 

Austro-Hungarian Epoch. 

The Austro-Hungarian epoch includes the distribution and his- 
tory of pellagra in that area extending from the Austrian Tyrol 
on the west, Poland on the north, southward and eastward to Bes- 
sarabia, Turkey, and Greece. The Austrian Tyrol lies to the north 
of and between Lombardy and Yenetia, and the development of 
pellagra here is principally an extension in point of time from 
these two regions. In 1875 to 1905 cases were numerous and 
severe, but at present show a decrease in number and in severity. 
I saw some of these pellagrins at Rovereto, a town in the Tyrol, 
at the foot of the Alps. Pellagra crossed the Transylvania Alps, 
which separate Hungary on the west from Roumania on the east, 
and appeared in the latter country about 1830. The elder Theodori 
assigned its first appearance to the year 1833, and the first patient 
was admitted in the hospital in 1846. It has continued to spread 
and increase in Roumania, which is divided into the two compart- 
ments of Moldavia and Wallachia. Felix, according to Hirsch 
(1878), estimated that there were 4,500 pellagrins in Roumania, 
not quite 1 per thousand of the whole population. Since that time 
the disease has constantly increased, and it is estimated that out 
of a population of 5,000,000 there are probably 75,000 pellagrins. 
Berger in 1888 found in the district of Gradisca, where he lived, 
790 pellagrins, 1.2 percent of the population. This district is in 
the western part of Austria, on the Italian frontier. It would 
seem that in the last twenty-five years the disease has constantly 
tended to decrease in the western part of Austria and to increase 
in the eastern part. It will be noted, too, that both of these areas 
are mountainous sections, the surface rolling in character, and in 
both sections corn is raised. According to Benjamin Triller 
(Thesis, Paris, 1906) the disease is also increasing in Servia and 
Bulgaria. Cases have been reported from Poland, southwestern 
Russia, Croatia, Dalmatia, Servia, Bosnia, and Herzegovina. 

Consul General G. Bie Ravendel investigated for me the preva- 
lence of the disease in Turkey, but found it so rare — comparatively 
unknown — that little definite information could be obtained. The 
disease is probably more prevalent in the rural sections of Turkey 
than has been known or reported. In Greece at the present time 
it is a rare disease, and is certainly not increasing. According 
to Consul General Gates, Athens, Greece, a case is occasionally re- 



60 PELLAGRA. 

ported, but chiefly from Thessaly in the mountains of northern 
Greece. Contrasting these two countries, Turkey and Greece, in 
respect to corn, it is found that in a good year in Turkey the corn 
crop amounts to from 140,000 to 160,000 tons, and in a bad year 
from 30,000 to 40,000 tons. On the other hand, in Greece, accord- 
ing to Consul General Gates, the amount of corn raised is neg- 
ligible, the principal crops being wheat and barley. The island 
of Corfu is off the western coast of Turkey, across the Adriatic 
from Italy. Information about pellagra in this island is furnished 
by Thypaldos. According to him the first appearance of the dis- 
ease was in 1839, but it became rather endemic in character, and 
in 1867 it prevailed in twenty-seven out of one hundred and 
seventeen rural communes in the island, the cases representing 
about 3.2 percent per one thousand of the population. 

Egyptian Epoch. 

Pellagra was first discovered in Egypt by Prunner, and he de- 
scribed it in 1847 under the heading "Leproses" as follows: 

"Pellagra is sporadic in Egypt, and such as we have studied 
it in Milan. We have seen three cases of it among the peasants, 
one of whom presents today, twelve years after our first seeing 
him, a brownish exanthem, paresis of the upper limbs, with re- 
traction and muscular atrophy." Up to the time of Sandwith this 
is the only reference made to the disease, except one by Dr. A. 
Figari Bey, who writes of a venereal disease in lower Egypt with 
"a kind of leprous pellagra." F. M. Sandwith, while at work on 
a paper on hookworm disease in 1893, became aware that some of 
his patients among the peasants, to use his own words, "were 
suffering with dermatitis, bald tongue, diarrhea, pains in the back, 
alteration of the knee jerk, insomnia, and melancholia, all symp- 
toms which could not legitimately be attributed to the anemia 
caused by the hookworm. ' ' It is, therefore, apparent that Prunner 
was right, even though so eminent an authority as Hirsch said that 
his description "does not by any means correspond to pellagra." 
The disease has, therefore, been in Egypt certainly for nearly 
seventy years and probably longer. It is far more extensive in 
Egypt, as outlined by the studies of Sandwith and Warnock, than 
has been supposed. The latter speaks of finding "scores" of pel- 
lagrous children. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 61 

According to Sandwith, pellagra in Egypt extends as far south 
as Assouan, or the tropic of cancer, latitude 24 degrees north. In 
1897, 178 cases were admitted to the Cairo hospital and the home 
of 164 determined. Of these 37 came from upper Egypt and 127 
from lower Egypt. Sandwith adds these two sentences: "The 
peasants in upper Egypt eat chiefly millet or sorghum vulgare, and 
not maize. The disease is said to be absent in Luxor, where no 
maize is eaten, but I saw several cases there. ' ' In 1891 Myles found 
it among the Arabs at Tokai on the Red Sea. In Egypt, as else- 
where, it is a country disease, and rare in such Egyptian cities 
as Port Said, Suez, and Alexandria. There is no polenta eaten in 
Egypt. Corn was brought from Syria into Egypt about 1840, and 
the peasants eat the variety called the camel's tooth, which is sown 
in July and ripe in November and December. According to Triller 
the disease has been found in Tripoli and in Tunis. Sandwith, 
during the South African war, found two cases among the lunatics 
at Robben Island, Cape Town, and he had previously recognized 
a third case in London which had been imported from South 
Africa. Physicians practicing in South Africa told Sandwith that 
they had never seen the disease in that section, but the two cases 
he found at Cape Town show that it exists there to a degree. Dr. 
W. M. Eaton, medical director of Rhodesia at Salisbury, Africa, 
states that "this disease has not been recognized in the territory." 

The meager facts at hand regarding the distribution and ex- 
istence of pellagra in Africa show that it is found at Cairo, in the 
parallel of latitude 30 degrees north, and at Cape Town, on the 
extreme of the African continent, latitude 34 degrees south. A 
further study and investigation in Africa would probably show a 
far wider distribution. I questioned very carefully in London the 
general agent of the African territory of Rhodesia, who is very 
familiar with the habits, customs, diseases, and foods of the people 
in that country, and, though I failed to gather from his very 
thorough description any evidence of the existence of the disease 
in Rhodesia, his opinion is borne out by Dr. Eaton quoted above. 
This is very interesting, too, in view of the fact that Rhodesia is 
an enormous corn-growing country. The samples shown me in 
London were the finest and largest ears, with the largest grains, 
I have ever seen. 

Two cases of pellagra have been reported as originating in the 
British Isles, but there is some difference of opinion as to whether 



62 PELLAGRA. 

the diagnosis was correct. At the meeting of the British Medical 
Association in 1898, Sandwith exhibited to physicians from India 
photographs of the Egyptian pellagrins, and three of these recog- 
nized the disease as existing in India. I have searched the records 
of the Indian medical congresses, bnt failed to find any reference 
to the disease. Dr. W. H. Jefferys, the coauthor of Jefferys and 
Maxwell 's ' ' Diseases of China, ' ' wrote me in response to an in- 
quiry as to the existence of pellagra in China: 

"My colleague, Dr. A. W. Tucker, suggested a long time ago 
that we should make a special point of looking out for pellagra 
in our Shanghai (China) clinic, and we did so and have never seen 
a case. Our clinic is a very large one, and represents Chinese 
from almost every province of the republic. Many of these pa- 
tients are not, of course, of the farmer class, so they bear little 
on the subject. 

"The Chinese eat practically no corn. I think this is a correct 
remark for all China. They grow a little for the use of foreigners 
in the treaty ports. 

"I have been misled far too often, and become very conservative 
about predicting that a disease does not exist in China, and, there- 
fore, I can not make such a statement. I can tell you, however, 
positively that pellagra has never been reported from China. Yet 
even that does not mean much, for I do not think that the average 
surgeon or physician would recognize pellagra unless on the lookout 
for it, or unless its great prevalence as a disease should force his 
attention. ' ' 

I have not been able to find any records of the existence of pel- 
lagra in Australia. Dr. Hubert M. Hewlett, of Fitzroy, Victoria, 
Australia, has been on the lookout for the disease in that continent, 
but has so far failed to find any record of it or any case of the 
disease. My friend, Mr. D. P. Mitchell, a mining engineer of 
Australia and a gentleman of exceptional powers of observation, 
told me that the disease was unknown there. 

American Epoch. 

This epoch includes the history and distribution of the disease 
in the western hemisphere, and naturally falls into two divisions: 

1. Pellagra in North America, including Mexico, Panama, and 
the West Indies. 

2. Pellagra in South America. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 63 

1. North America. — Pellagra was first discovered and reported 
in America in 1864 by Dr. John T. Gray, of Utica, N. Y. A 
second case was reported verbally at the same time by Tyler, of 
Summerville, Mass. There have been speculations as to pellagra 
existing among the soldiers during the Civil War, but this is a 
matter of doubt. In 1883 Sherwell, of Brooklyn, reported a case 
in an Italian sailor, and in 1889 Bemis, of New Orleans, diagnosed 
a case of pellagra in that city. From all the evidence it is probable 
that the disease existed in the Carolinas and in Georgia in the 
early eighties, though the cases were not diagnosed as pellagra and 
the disease itself was unknown. Sherwell reported another case 
in New York in 1902. These cases thus far referred to seem to 
have been sporadic or imported cases, but it is probable that the 
number of cases of pellagra in the United States has been increasing 
since 1890, and that the disease has existed in the United States 
since 1880. 

It is interesting to know that Sandwith, in Egypt, while study- 
ing hookworm disease, discovered pellagra in that country in 1893. 
At this time he suspected the existence of pellagra in America, 
thinking that it "might exist unrecognized in the South, and at 
one time I requested my friends to put me in communication with 
the poorest folk of the maize-eating district. I was referred to a 
settlement in eastern Virginia for pauper negroes, but on investi- 
gation I found that the inmates lived in stone houses on pork 
rations, and I came to the conclusion that the word poverty repre- 
sented no condition in America which could compare with the 
misery of the impoverished peasants of Italy, Roumania, or Egypt." 

Seven years later, while in South Africa, Sandwith saw two 
cases of pellagra and again suspected the disease in the United 
States. The real beginning of the history of pellagra in North 
America and the discovery of the present epidemic began just as 
the real discovery of pellagra in Egypt began — by the study of 
hookworm disease. H. F. Harris, of Atlanta, reported "A Case 
of Hookworm Disease Presenting the Symptoms of Pellagra." In 
1907 George H. Searcy reported an epidemic of pellagra at the 
Mt. Yernon, Alabama, asylum for negroes. This epidemic existed 
during the years of 1906 and 1907. Babcock and Watson diag- 
nosed the disease at the state hospital for the insane at Columbia, 
S. C, and their report marks the beginning of widespread interest 
in the disease in North America. In 1908 they studied the disease 



64 PELLAGRA. 

in Italy, and identified American and Italian pellagra as one and 
the same disease. Their reports aroused the attention of physi- 
cians throughout the country, and to them is due the arousal of the 
attention of the profession in the southern states. 

Assistant Surgeon C. H. Lavinder, of the United Hospital and 
Marine Service, studied the malady, and later Captain J. F. Siler 
and Captain Henry J. Nichols, of the medical corps of the United 
States army. Under the auspices of the State Board of Health 
of South Carolina a conference on pellagra was held in October, 
1908, and a national conference on pellagra was held in South 
Carolina at Columbia in 1909. Surgeon C. H. Lavinder, Dr. J. 
W. Babcock, J. J. Watson, Zeller of Illinois, and Bass of New 
Orleans have written many articles on the disease, which have 
been helpful to the physicians in this country. Pellagra in 
America has increased very rapidly, especially in the southern 
states and in the Mississippi valley, during 1908 to 1911, and it 
is probable that the spring of 1912 will show an influx of new 
cases. The type of the disease so far has been more severe, more 
acute, of shorter duration, and higher mortality than in Italy, 
Roumania, or Egypt. The percentage of males is less in proportion 
than in Italy. For example, in the state of Tennessee, out of 316 
cases 214 were females and 102 males, and in three counties in 
southeastern Kentucky out of 140 cases 111 were females. 

The map on pages 72 and 73 shows the distribution of pellagra in 
North America. Much of the area where pellagra is endemic is 
not in the official registration area, and many of the statistics are 
merely estimates. The United States Census Bureau for 1910 re- 
ports 368 deaths from the disease in the bureau's registration area, 
and of these 71.5 percent were females. This, however, does not 
nearly represent the number of deaths in that year in the United 
States from the disease, since most of these occur in the country 
districts and are not reported at all, either to country, state, or 
national authorities. The census gives 69 deaths as occurring in 
Atlanta, Ga., more than occurred in any other city in the United 
States. As a matter of fact, hardly any of these cases originated 
in the city of Atlanta, but most of them came from the smaller 
towns and adjacent rural districts, and should really be classified 
as imported cases so far as the statistics of the city of Atlanta are 
concerned. 

The states of the Union, according to reports received in 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 



65 



'-%««*£ *-=- -'-"-- 




r,r-r. _ _ _ _ _ • - - 

II [ ) < i ijjn. j / . t a U u [ ■ i 

B5 I jill 1 .'.'I p^ 1 1 1 j| n f| « 

** a ''Lrndtf"^ ~"^*3k. V , *L. ,,, 1 1 'I 

Fig. 6. — Pellagrosario at Rovereto, Austria, with the Alps in the background. A govern- 
ment institution for the treatment of pellagra, and only pellagrins are admitted. Dr. 
Probitzer is the director of the institution. This place was visited by the author in 
October, 1911. 

November, 1911, as to the prevalence of pellagra in them, are here 
given : 

Pellagra in the States. 

1. Maine „. . » . 1 case in the state hospital for the insane. 

2. New Hampshire. . . .No cases reported. 

3. Vermont 1910, 2 cases in Addison county; both fatal. No 

cases since. 

4. Massachusetts 1910, 3 cases. No report since. 

5. Connecticut No cases. 

6. Rhode Island 1910, in insane hospital, 7 cases, with 4 deaths; 2 

males and 2 females. All these insane. 

7. New York 1911, 2 cases, with deaths. These were imported 

cases. 

8. New Jersey 1910, 1 case; 1911, 1 case in Somerset county. 

9. Delaware No cases reported. 



66 PELLAGRA. 

10. Pennsylvania January, 1911, to November 1, 1911, 8 new cases. 

11. Maryland To January 1, 1911, 11 cases; from January 1, 

1911, to October 1, 1911, 8 cases. Of the 1911 
cases, 7 died and 1 showed improvement; 6 were 
white and 2 were colored; 6 females and 2 males. 
The case that improved was a negro girl 5 years old. 

12. Dist. Columbia 1911, 2 cases; 1 death. 

13. Virginia 1910, 350 cases. During 1911 there were not as 

many, but no estimate. 

14. West Virginia 1 case. 

15. North Carolina. ... 1911, during the first eight months there were 69 

white and 40 colored deaths reported to the State 
Board of Health from pellagra from a registration 
area with a population of 348,057. This area in- 
cludes all towns of over 500 inhabitants. Estima- 
ting the mortality at 20 percent, we have a total 
number of cases in North Carolina of 545. 

16. South Carolina .... Estimated, 1,000 cases. 

17. Georgia Estimated, 2,500 cases. 

18'. Alabama Disease increasing. Estimated, 2,000 cases. 

19. Mississippi Disease increasing. Estimated, 2,000 cases. 

20. Florida At the close of 1910, 99 cases reported. Estimated, 

250 cases. 

21. Louisiana In June, July, and August, 24 deaths were reported. 

Estimated, 500 cases. 

22. Kentucky Estimated, 500 cases. Specially prevalent in the 

mountain counties in the southeastern part of the 
state. Assistant Surgeon R. M. Grimm found 140 
cases in the three counties of Whitley, Knox, and 
Bell. 

23. Tennessee Pellagra prevails in sixty-seven out of the ninety- 

six counties in the state; 316 cases in these coun- 
ties. Out of the sixty-seven visited, number of 
cases in the state estimated, 500. (See Report 
of Pellagra Commission appointed by the Tennessee 
State Board of Health.) 

24. Texas July, 1911, 33 deaths from pellagra, and 35 deaths 

in August. Estimated, 1,500 to 2,500 cases. 

25. Arkansas Disease increasing. Conservative estimate, 1,000 

cases. 

26. Kansas First 10 months of 1911, 8 cases; 2 fatal. Disease 

increasing. 

27. Missouri Estimated, 10 cases. 

28. Oklahoma September 30, 1911, 19 cases and 13 deaths. 

29. Nebraska No cases reported. 

30. Ohio February, 1910, 1 case at Ironton, O.; May, 1911, 1 

case at Cortland, O. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 67 

31. Illinois 1909, 192 cases, all in hospitals for the insane; 1910, 

78 cases in hospitals and 5 outside; 1911, 48 cases 
in hospitals and 9 outside. Report of special com- 
mission to be published in 1912. 

32. Indiana 1 case reported, with death. Insane hospitals have 

been carefully searched for the disease, but no cases 
found. 

33. Iowa 1910, 3 cases; 1911, 1 case. 

34. Wisconsin 'No cases originating in the state ; 1 case in spring 

of 1911 in Milwaukee and 2 deaths in September, 
1911, but these 3 cases contracted the disease in 
the southern states and went north Avith the hope 
of obtaining relief. 

35. Michigan No cases reported. 

36. Minnesota No cases reported. The state institutions, especially 

* the hospitals for the insane, have been carefully 
searched and no cases found. 

37. North Dakota No cases reported. 

38. South Dakota No cases reported. Probabty present, but not identi- 

fied. 

39. Montana No cases reported. 

40. Wyoming No cases reported. 

41. Colorado ..Previous to July, 1911, no cases reported. In July, 

1911, 5 cases reported, and in August, 1911, 4 cases. 

42. New Mexico No cases reported. 

43. Idaho No cases reported. 

44. Arizona To November 1, 1911, 3 deaths reported in the terri- 

tory; 8 cases unofficially reported in 1910. No 
new cases in 1911. 

45. Utah No cases reported. 

46. Nevada No cases reported. 

47. Washington A sporadic disease, with 3 cases, reported. No cases 

in the asylums for the insane. 

48. Oregon 1 case reported, and this a patient coming from one 

of the coast counties in Washington. Case rapidly 
fatal. 

49. California First case reported in 1909, only 4 cases reported all 

told, with 2 deaths in 1910. There are probably 
more cases in California. 

From these figures, out of the forty-nine states, including the 
District of Columbia, pellagra has originated and prevailed in 
thirty-three. This count of thirty-three does not include a state 
like Oregon, for instance, where pellagra was imported, but did 
not originate within the state. It is apparent that the disease ex- 
tends from Maine to California, and that there is a skip in that 



68 PELLAGRA. 

tier of states beginning with Montana on the north, extending 
southward through Idaho, "Wyoming, Utah, Colorado, Arizona, and 
New Mexico. The disease, however, reappears in the three Pacific 
coast states, but does not seem as yet to have originated in Oregon. 
It is interesting also to note the presence of the disease in Illinois and 
its extreme rarity in Indiana and Ohio. Again, Wisconsin, Min- 
nesota, and the Dakotas are a nonpellagrous territory. The disease, 
therefore, may be classed as sporadic in the New England and 
middle Atlantic states, epidemic in the southern states, and sporadic 
again on the Pacific coast. 

It is probable that there are 10,000 cases of pellagra in the United 
States at the present time. These statistics were furnished by the 
different State Boards of Health throughout the country. 

1 have collected by means of return postal cards more detail 
facts concerning the distribution of pellagra in the state of Georgia. 
Topographically, this state may be divided into three sections. The 
northern, hilly and mountainous; the middle third, hilly, rolling 
country; and the lower third, flat. Pellagra is least prevalent in 
the southern part of the state and the number of cases increase 
toward the north. There extends across the state from Columbus 
through Macon to Augusta on the eastern border a line which is 
presumed to divide the northern hilly portion of the state from the 
southern portion, which partakes more of the nature of a coastal 
plain, and by far the majority of these cases originate north of 
this fall line. 

Counties in the Northern Third of the State. 

County. Cases. Deaths. Condition. 

Polk 75 25 Disease increasing. 

Gordon 20 3 Disease increasing. 

Clark 200 1 50 2 Disease increasing. 

Fannin 12 4 Disease increasing. 

Stephens 10 2 Disease not increasing. 

Habersham 50 45 Disease increasing. 

White '. 8 3 Disease increasing. 

Cobb 15 153 Disease increasing. 

Madison 12 6 Disease not increasing. 

DeKalb 150 50 Disease increasing. 

1 Two hundred cases in three years. 

2 With possibly 50 deaths. 

3 Fifteen deaths in last three years. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 



69 



Middle Thied of State, 

County. Cases. Deaths. 

Newton 5 6 

Muscogee 100 25 

Henry 14 

Cla} T ton 3 

Monroe 30 12 

Meriwether 10 

Taliaferro 4 45 

Greene 25 5 

Heard 5 5 



Condition. 
Disease not increasing. 
Disease increasing:. 



Disease increasing. 



Southern Third of State. 

County. Cases. Deaths. 

Colquitt . 2 

Worth 6« 

Berrien 5 

Dodge None 

Decatur 6 8 

Pulaski None 

Burke None 

Randolph 10 39 

Coffee None 



Condition. 



4" Disease increasing. 



2. Mexico. — The mortality statistics for the city of Mexico for the 
eleven years 1900 to 1910 give 1 death from pellagra, which oc- 
curred in the sixth district of the city in 1909. The physicians and 
hospitals for the city of Mexico have not had any cases. A death 
from pellagra occurred in the city of Monterey, Mexico, in 1910. 
This patient was a physician who formerly lived in the United 
States, but he probably developed the disease in Mexico. Dr. 
George McDonald, Avho formerly lived in Mexico in the section 
around Monterey, told me that since coming back to the states he 
remembers three cases in his practice in Mexico who were strangely 
diseased, but that he is convinced now that they were cases of pel- 
lagra. The disease has prevailed quite extensively in Yucatan, a 
province in the southern part of Mexico. Pellagra developed there 



4 No cases at present. 

5 Four deaths in last three years. 

6 Probably 20 cases in the county. 

7 Four deaths in 1910. 

8 Six cases in last few years. 

9 Three deaths in last three years. 



70 



PELLAGRA. 




Pig. 7. — Group of eight boys, all pellagrins. (Photograph by the author on the steps of 
the pellagrosario at Inzago, near Milan, Italy.) 







Fig. 8. — A closer view of three of the boys shown in Fig. 7. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION. 71 

between 1882 and 1891, and was very prevalent in 1907 and 1909. 
Ganmer is probably mistaken when lie says that from 8 to 10 percent 
of the population are affected with the disease. Pellagra has, 
therefore, existed in the city of Mexico, Monterey, and Yucatan, 
and it is probable that an investigation of the disease in Mexico 
would show that it is more prevalent than is supposed, especially 
in the northern and central parts. 

There is no positive evidence as to the existence of the disease 
in Central America, but Dr. John L. Phillips, under date of 
November, 1911, writes: "Pellagra was first diagnosed on the 
Isthmus of Panama in October, 1909. Since then we have had 32 
cases, with 16 deaths." These statistics were collected by Dr. 
Phillips in the sanitary division of the Isthmian Canal Commission 
and are accurate. Pellagra probably prevails, therefore, through- 
out Central America in all that region north of Panama. The 
disease is also found in Jamaica, and occasional cases develop in 
Cuba, Porto Pico, and many cases occur in Barbados. 

3. South America. — The existence of pellagra in South America 
is doubtful. Information regarding cases in Peru, Brazil, and 
Argentina is lacking, but one would not be surprised to find the 
disease more widespread in South America than evidence shows. 
I have searched the reports of the congresses on sanitation of the 
American republics, but I have failed to find any reference to or 
mention of pellagra. It is probable that the disease exists in 
Colombia, Venezuela, and Ecuador, though much positive infor- 
mation is needed for all this continent. 




Fig. 9. — Map showing distribution of pellagra in the world. 




^ 



Pellagra not reported. 
Pellagra sporadic — few cases. 
Pellagra prevalent. 



,A 



^ 



C E 



4? 



- v> 



Note relatively small pellagrous area. 






CHAPTER III. 

CLASSIFICATION. 

Pellagra is a general disease, and in our nomenclature it should 
be classed as such. It is a systemic disease, and not a system 
disease; a disease of the whole organism, and not a disease of any 
one system of organs. It is net a skin disease, because it also 
affects and produces organic changes in the nervous and gastro- 
intestinal systems. It is not a disease of the nervous system, be- 
cause it affects the cutaneous and digestive systems. It affects 
the nervous system as much as, if not more than, the digestive 
system, and therefore it can not be classified as a gastrointestinal 
disease. In Italy it is somehow preferably placed in dermatology, 
probably because the skin symptoms are so noticeable and have 
received so much attention. 

Up to 1884 the Royal College of Physicians of London classified 
it as a skin disease, but since 1896 it has found a home among 
general diseases. It is no more a skin disease than syphilis or 
typhoid fever, though both of these have eruptions which help 
to confirm and to decide the diagnosis; it is no more a gastro- 
intestinal disease than yellow fever or tuberculosis, though both 
of these involve the abdominal organs; it is no more a nervous 
disease than sleeping sickness or leprosy, though both of these 
involve the nervous system seriously. Pellagra leaves its mark 
everywhere — on bone and parotid gland, cord and intestine, skin 
and stomach. It is a general disease, with a systemic pathology. 

OTHER INFECTIONS IN PELLAGRA. 

The tissues of a pellagrin offer fertile soil and little resistance 
to infection by bacteria, protozoa, and worms. Pellagra draws 
generously on the natural reserve force of all the organs, and it is 
natural to find several infections associated with the disease. The 
advance of tropical medicine has shown that the pellagrin is fre- 
quently a hospitable host to more than one parasite, and that the 
cachectic power of pellagra is aided by the blood extracting power 

-74 



CLASSIFICATION. 



75 



of several varieties of worms. Harris, studying ankylostomiasis, 
first discovered pellagra in Georgia, and Sandwith had the same 
experience in Egypt. The first record I can find of the presence 
of parasites in a pellagrin is in the elder Strambio's work on 
"De Pelagra." In case 9, at autopsy, he records "20 lumbrici in 
stomach and 7 in esophagus." 

I have been surprised at the similarity in distribution of pellagra, 
uncinariasis, and malaria; and, since other intestinal parasites and 
protozoa are common in temperate and tropical climates along 



r - '•- 


. i 


* * *•*«%«, % „ M\ 


» w ■ '^BBJ KT#: : , g|H ***' W 


m 


1 n 



Fig. 10. — Pellagrous "boy. Very stupid, with vacant expression ; body thin and gaunt. 
(Photograph by the author in Italy in 1911.) 

with these diseases, pellagra is found associated with as many as 
three infections in the same patient. Pellagra by itself is serious 
enough, but pellagra associated with other infections endangers the 
patient far more. Pellagra diffused throughout the system, and 
hookworm inside removing constantly "the blood thereof which is 
the life thereof," causes darker clouds to rise on an already clouded 
prognosis. Amebic dysentery is found throughout the tropics and 
in parts of the temperate zone ; in the United States it is the most 
common variety cf all dysenteries. Pellagra involves the whole 
gastrointestinal tract, and, of course, would tend to increase an 



76 



PELLAGRA. 



infection with amebas, and an amebic infection would tend to cause 
the pellagra to make greater inroads. Much attention has been 
given to amebic infection in pellagrins in the United States, but 




Fig. 11. — 'Two Georgia cases, presented by the State Hookworm Commission. The smaller 
boy, aged 4 years, has had pellagra two years, and is also infected with hookworm ; 
dry, wrinkled skin on hands, feet, and legs; marked diarrhea, rather constant; in- 
continence of urine and feces when picture was made ; anxious, drawn, old-age 
expression of face ; marked physical weakness and mental apathy. The larger boy, 
aged 7 years, has had same duration of symptoms, though less severe ; skin eruption 
is slightly worse than that of the smaller boy; there are epithelial and blood cells in 
the feces, and the hookworm disease is present. 




Fig. 12. — Same case as shown in Fig. 11. Side view, showing the protruding abdomen. 

the prevalence ot amebic dysentery in this country, plus the recur- 
rent inflammation of the mucosa in pellagrins and the general 
lowered resistance, tends to explain the association of the two 
infections. 



CLASSIFICATION. 77 

The following interesting table from Sandwith's Egyptian cases 
shows uncinariasis and bilharziosis in pellagrins during 1895, 1896, 
and 1897 : 

Not Remain- 

Cured. Relieved, relieved. Died. ing. Total 

Pellagra and uncinariasis... 50 184 18 8 23 283 

Pellagra, uncinariasis, and 
bilharziosis 19 99 3 9 24 154 

This is a general death rate of 4.3 percent after deducting the 
cases still in the hospital, 6.9 percent for patients attacked by all 
three diseases, and only 3 percent for patients attacked by only 
two diseases. It seems that the additional infection by bilhar- 
ziosis doubles the danger and the death rate. Of course the treat- 
ment of uncinariasis is far easier and more satisfactory of the two 
associated infections, and even a pellagrin shows marked improve- 
ment after the hookworms are gone. 

Willetts, formerly pathologist to the Georgia State Sanitorium, 
examined the feces of 500 unselected insane negro females, and of 
these 35 were pellagrins ; of the total number 250, or 50 percent, 
were infected with some form of intestinal parasite ; of the 35 
pellagrins, 14, or 20 percent, were so infected. Trichuris and 
ascaris predominated in the whole number, and strongyloides and 
uncinaria in the pellagrins. 

Strongy- 
Trichuriasis. loides. Uncinaria. Hymenolepis. 

40.2 18.2 11.8 0.2 



Number 
examined. 

500 


Infections. Ascaris 
250, or 28.2 




50 percent 


Number 

of these 

pellagrins 

35 


14, or 8.57 




40 percent 



17.14 25.71 20.0 2.86 



Pellagrous children especially are apt to have hookworm and 
pinworm infections. The former may occur in pellagrins having 
only a mild attack, but hookworm disease is to be considered an 
enfeebling factor in pellagra, and some of the symptoms attributed 
to it — as anemia, emaciation, and weakness — may, in part at least, 
be due to the worms. This also applies to malaria, alcoholism, 
syphilis, tuberculosis, frequent pregnancies, surgical operations, or 
any condition of disease or stress that lowers resistance and invites 
prevalent disease of any kind. It is plainly true that with all the 



78 PELLAGRA. 

members of a family equally exposed to the cause of pellagra, ex- 
isting infections present in certain debilitated individuals act as 
predisposing factors to pellagra, and these individuals will develop 
the disease more easily than their strong and healthy relatives ; and, 
vice versa, once pellagra is developed, other infections will more 
easily gain a foothold. Favus seems to have a preference for the 
scalps of Egyptian pellagrins. The physician often observes in 
poor children a paleness and lack of color and vivacity, due not to 
food nor to any disease, but to an absolute lack of food; it is the 
cachexia of indigence, and in endemic pellagrous districts predis- 
poses to the disease. 

Nichols' researches at the Peoria (111.) Asylum for the Insane 
enabled him to prepare the following very interesting table on 
protozoan infection in pellagrins, and to compare it with nonpella- 
grous inmates and soldiers in the Philippines. 

Pellagrous Nonpellagrous Soldiers in 

inmates. inmates. Philippines. 

Number examined 88 101 454 

Negative 14.7 percent 51.4 percent 48.8 percent 

Amebse 37 11 16 

Flagellates (alone) 20 12 34 

Encysted protozoa (alone).. 27 24 

Percent of cases with protozoa 85 48 51 

The excess of protozoan infection in pellagrins is here very 
noticeable, being 37 percent greater than in the nonpellagrous in- 
mates, and 34 percent greater than in the soldiers living in the 
tropical Philippines and subject to far greater changes in diet and 
variations in climate. Babcock and Lavinder found protozoan in- 
fections in pellagrins in South Carolina, and I have observed 
amebae in a highly cultured woman with pellagra of several years' 
duration. The diarrhea in her case was persistent and more pro- 
nounced than any diarrhea I have seen. On autopsy of 18 of the 
pellagrins included in the above table, Siler and Nichols found 
ulcers in the colon in 12, or 66 percent, and 1 pellagrin "died of 
peritonitis following a perforation of an amebic ulcer;" 2 had 
tubercular ulceration and 1 trichinosis. In 1 case oxyuris eggs were 
found, but no uncinaria. 

Siler and Sambon, working together in Italy, found ankylos- 
toma duodenale, which is the European species of hookworm corre- 
sponding to the necator Americanus of Stiles, the most common 



CLASSIFICATION. 79 

intestinal parasite in Italian pellagrins. Pisenti and Mandolesi 
state that those pellagrins who present the most severe anemic and 
oligemic symptoms "were those who presented the greatest number 
of hookworm eggs in their feces." Pellagra causes anemia, but 
the profound anemia in pellagrins necessitates the examination of 
the feces for hookworm ova. In the southern states it should be the 
first step in the treatment of pellagra. 

Besides the hookworm, Sambon found ascaris lumbricoides, 
trichuris trichiura, oxyuris vermicularis, cercomonas hominis, 
ameba coli, and in one case the ova of hymenolepis nana. Strongy- 
lcides intestinalis is also found in Italy as well as necator Ameri- 
canus. Summarizing the varieties of intestinal parasites found in 
pellagrins in Egypt, Italy, and America gives the following results : 

America. Italy. Egypt. 

Ameba coli -\- 

Ankylostoma duodenale 

iSTecator Americanus -\- 

Trichocephalus hominis -{- 

Oxyuris vermicularis -|- 

Cercomonas hominis — 

Hymenolepis -)- 

Schistosomiim — 

Bilharziosis — 

Strongyloides -(- 

Flagellates '. -(- 

Trichina spiralis -j- — ' — 

Ascaris lumbricoides -j- -\- — 

The plus mark (-|-) indicates presence, and the minus mark ( — ) 
indicates absence. Some forms marked absent are probably pres- 
ent, but not reported. Intestinal parasites in pellagrins deserve 
a more detailed study, and its importance in treatment will become 
more apparent in view of the wide distribution of hookworm disease 
in the southern states. Either disease produces lassitude, weak- 
ness, dwarfism, anemia, emaciation, senile and wrinkled skin, dizzi- 
ness, headache, gastralgia, stupid expression, and mental inertia. 
Pellagra is more susceptible of treatment after removal of hook- 
worm infection. Both diseases are rural in origin, common among 
farmers, and with the same general geographical distribution ; often 
to be found aggravating each other in the same individual, and 
their association may be expected in many cases. 



+ 


+ 


+ 


+ 


+ 


+ 


+ 


+ 


+ 


— 


+ 


— 


— 


+ 


— 


+ 


+ 


— 


+ 


+ 



80 PELLAGRA. 

RELATION OF PELLAGRA TO THE SEASONS. 

Pellagra is a disease which avoids the winter. It usually first 
appears in the spring and early summer; it may reappear in the 
same patient in the autumn months of September or October, but 
usually it omits the autumn advent, hibernates during the winter, 
and recurs the following spring. In Italy the majority of the 
spring attacks occur between the middle of March and the middle 
of May, with extremes of invasion as early as February and as late 
as June. The autumn invasion recurs during September and 
October, with extremes of an early limit in August and a late limit 
in November. The latitude of 40° cuts the pellagrous area of Italy 
into northern and southern halves. 

The pellagrous area of Egypt is cut by the latitude of 26° north, 
and therefore is about 1,000 miles south of the Italian area. The 
spring attack occurs from November to March ; the majority of the 
cases make their advent and reach their acme during January and 
February. Few cases recur during the summer. The Egyptian 
climate is far more tropical than either the European or American, 
and January more nearly corresponds to spring in the latter two 
countries. In North America the pellagrous area is included be- 
tween 25° and 45° north latitude, though by far the greatest num- 
ber of pellagrins live in the belt on either side of the line 35° north 
latitude. 

In Florida the spring invasion may occur as early as December 
and January, as in the case reported by Randolph; coming north 
into south Georgia, the spring attack may begin in February, and 
the farther north the later the seasonal attack. These represent 
the early appearances of the malady, but as a rule the greater 
number of cases in the southern states occur in April, May, and 
June. What is most surprising and apparently different from the 
usual cases described in the Italian and French literature is that 
the onset in America varies from January in Florida to late 
October, and one case is reported as recurring in November. I have 
seen cases whose onset included every month in the year except 
November, December, and January. One reason for this is the mild 
climate in the South, with only two or three months that could be 
counted severe, and even then the severity is not continuous. 

Again, spring advances in this large country gradually, so that 
a 200-mile trip produces quite a change in climate and in the time 



CLASSIFICATION. 81 

of advent of the seasons. As a rule, pellagra is synchronous with 
spring, recurring earlier in the year if the winter is mild and spring 
early, and later if the winter is severe and the spring late. Of 45 
cases collected by Tucker of Virginia, 4 cases began in the summer, 
4 in the spring, 2 no time given; of the 45 who gave the months, 
2 began in January, 2 in February, 10 in March, 9 in April, 7 in 
May, 9 in June, 4 in August, 1 in October, and 1 in November. 

It is important to remember that there are greater variations in 
the time of the first onset than in the time of the subsequent attacks. 
In America the first invasion of the disease may come in any month 
from late February to October, with an occasional case in January 
or November, but the recurrences are more periodic and uniform, 
and come with a vernal regularity. Case 3 in Chapter I (page 25) 
illustrates this uniform recrudescence in the spring. The autumn 
recurrences are practically limited to September and October, a 
more narrow limitation than obtains in the spring, and the autumn 
attack probably in a majority of cases fails to appear. One of 
the essential elements in the knowledge of the disease is the ability 
to diagnose pellagra in the fall or winter, when the disease concels 
itself in the winter sleep. I have seen one case, about to recur in 
October, where the prodromes of epigastric uneasiness, slight diar- 
rhea, vertigo, and weakness recurred, but no dermatitis, and in a 
few days the woman seemed strong and well. It is probable that 
if the disease in this case had taken deeper root and been more 
advanced, there would have been a typical autumnal recurrence. 

INCUBATION PERIOD. 

The period of incubation of a disease includes the time between 
the intake of the poison or the infecting agent and the actual onset 
of the disease. This incubation time consists of two stages: (1) 
the stage immediately after the infection or the intoxication, in 
which there are no external symptoms, as in the two to four days 
following the exposure of a child to scarlet fever; (2) the stage 
of prodromes, during which symptoms appear which are premoni- 
tory of the disease, as the appearance of sore throat before the 
actual onset of scarlet fever. The determination of the incubation 
period is not difficult when the cause of a disease is well known, 
because then the time of infection or exposure can be accurately 
ascertained. It is altogether different in pellagra, for the simple 



82 



PELLAGRA. 



reason that we do not know the cause, and therefore the incubation 
period is more or less a matter of a priori reasoning and specula- 
tion. Furthermore, the prodromal symptoms differ so widely in 
degree and in kind that even now the initial symptoms, not to 
mention the initial symptom, are still a matter of dispute. The 
prodromal symptoms vary from constipation to diarrhea, vertigo 
to dermatitis, and slight stomatitis to actual nausea. 

It is evident that if an infant is born healthy, and develops 
pellagra during early infancy, the incubation period is slightly less 
than its age. Pellagra in a 5-months' infant previously healthy 
indicates an incubation period of less than five months. Further- 
more, if a disease habitually makes its appearance in the early 
spring both in its first and subsequent attacks in the same individ- 
ual, it is evident that the exposure to the intoxicating or infecting 
agent must be near the early springtime, or the intoxicating agent 
must be strangely and unaccountably cumulative at this time. In- 
fants are peculiarly susceptible to intoxications, as indicated by milk 
poisoning, and to infections, as indicated by the various infective 
diseases common to childhood. 

I have not been able to find in America pellagrous infants under 
one year, with one exception, but Sambon found infant pellagrins 
in Italy, and their ages reduce the previously estimated time of 
incubation. One infant was born in an Italian jail and nursed by 
its mother until 5 months old; it was then taken away and given 
to peasants living in the country. It developed pellagra in two 
weeks, or at 5y 2 months old. Another infant was born in Novem- 
ber, and taken into the fields about the middle of March; it de- 
veloped the pellagrous dermatitis in May. One of these developed 
the disease about April 1st and the other about May 15th. The 
incubation period in intoxications, such as meat and mushroom 
poisoning, ergotism, ice cream, and canned goods, is short, varying 
from twelve hours to a week, and usually near twelve hours — 
longer, of course, in ergotism. The time of incubation in infectious 
diseases is notably short, as in typhoid, cholera, malaria, smallpox, 
and influenza. Considered either from the history of the two in- 
fants given, or intoxications and infections in general, there is 
reason to believe the incubation period in pellagra varies from two 
weeks to two months, and probably nearer two weeks. 

Another reason that complicates our knowledge of the disease is 
the insidious onset of pellagra. It insinuates itself into the system, 



CLASSIFICATION. 83 

and even an intelligent pellagrin hardly knows from the prodromal 
symptoms how or when it started. Sandwith in Egypt, and Lud- 
wig Merk studying in Austria and Italy, believe the incubation 
period to be from seven to nine months. Sandwith believes the 
poisoning due to corn from the previous year's crop, and the incuba- 
tion probably as long as twelve months. 

The corn crop is harvested in Egypt in November and December, 
and the majority of Egyptian pellagrins begin their eruption in 
January. He does not think sufficient fungi or poison could de- 
velop in this time to cause pellagra, and therefore makes the criminal 
out of the previous year's crop. This reasoning appears incorrect 
in view of corn as a cause. 

Incubation is considered to end with the dermatitis, and, as fever 
is practically absent in the initial attack of pellagra, the erythema 
marks the close of the prodromal symptoms, and usually the 
definite onset of the disease. There may be no prodromal symp- 
toms, and the dermatitis ushers in the attack. 

DURATION OF PELLAGRA. 

The duration of pellagra depends on the severity of the symp- 
toms and the rate of progress of the disease. It is a chronic disease 
as a rule, but it occurs as an acute disease occasionally, and mid- 
way between these is a third form of moderate length. It is better 
to say that it is a disease of relatively long standing, whether the 
attack be acute or chronic. For instance, the acute form may last 
six weeks or three months, but this is unusually long for the aver- 
age acute attack of a disease. Classified according to time, three 
types are found: 

1. Acute Pellagra. — Malignant pellagra characterizes this at- 
tack. It lasts from one week to three months, and progresses 
rapidly to a conclusion. Fatal as a rule. It is also called typhoid, 
florid, tetanic, or fulminating pellagra. 

2. Subchronic Pellagra. — Lasts not over two years and ends in 
death or recovery. Two subdivisions : 

(a) Mild Subchronic Pellagra, or Convalescent Pellagra. 
There are one or two mild attacks, ending in recovery without sub- 
sequent recurrence. Pellagrous Italian boys, after one or two mild 
attacks, may develop into healthy men, and be accepted as soldiers 
in the Italian army. 



84 PELLAGRA. 

(b) Severe Subchronic Pellagra, or Cachectic Pellagra. 
From the first attack there is rapid emaciation, the symptoms are 
pronounced, and cachexia comes quickly. There are no intermis- 
sions as in the chronic form, and death ensues in two years or less. 

3. Chronic Pellagra. — This is the usual type in point of time, 
and it may last from three to thirty years, recurring regularly 
each spring or at longer intervals. It is mild and slowly pro- 
gressive. It may end in apparent recovery, in insanity, or in death. 
Patients with this type are often not incapacitated from work, 
and may be apparently healthy during the seasonal intermissions 
of the disease. 

Pellagra is too variable a disease to permit hard and fast lines 
of classification, and, as in nearly all diseases, different types grade 
insensibly into each other in actual practice. The chief features 
of the acute form are its rapid onset, high fever, and quickly fatal 
ending, but acute pellagra may terminate in either the severe sub- 
chronic pellagra or even the chronic form. The chronic form may 
occur for three successive years, disappear from external appear- 
ances, only to reappear in from three to six or ten years. In the 
same patient the disease may appear for several successive seasons, 
and then disappear for an equal time or longer. 

There are problems that arise from this behavior of pellagra that 
are at present unsolved. Does reinfection or reintoxication account 
for the chronicity of pellagra? Is there a latent pellagra that 
explains its disappearance in a patient pellagrous for a number 
of years, or does reinfection account for the reappearance of the 
disease? Malaria is a disease which may appear as a result of 
long-standing latency, or as a result of reinfection. An individual 
moving from a malarial area to a more healthy center may for one 
or two springs have a malarial attack due to a latent infection, with 
subsequent improvement in health. He may return to the endemic 
malarial area and have a reinfection. Pellagra offers a stronger 
evidence of latency than malaria, for it is certainly latent from 
season to season, as it appears in the spring and disappears until 
the following spring, even if the patient is removed from the en- 
demic area and no longer eats any of the products of maize. Since 
it is latent from season to season, it is reasonable to believe that 
it is latent for longer periods. Jansen, in 1788, saw the disease 
in Milan, and, referring to the end of the spring attack, writes : 
"The patients, however, are not now to be considered well; the 



CLASSIFICATION. 85 

disease hides itself, but is not eradicated, for no sooner does the 
following spring return, then it quickly reappears." Strambio 
says pellagra, concealed after several successive seasonal attacks, 
"is a snake in the grass.' 7 There is no reason for doubting the 
fact that reinfection recurs, and especially is this true if residence 
in an endemic center is continued. 

Strambio, in 1787, found the length of the disease from onset 
to death in 10 pellagrins — 7 men and 3 women — averaged five years 
and seven months, ranging from three months in the lowest to 
twenty years in the highest. Sambon found octogenarians in Italy 
who had "donned the pellagrous bloom since childhood." I have 
found one North Carolina case with a clear history of duration of 
about twenty years, and, while the disease has been epidemic in 
the United States for an unknown period, probably not longer than 
twenty years, many physicians can make a backward diagnosis of 
pellagra in former patients with a course of from fifteen to five 
years. In Egypt the peasant pellagrin or fellah does not apply for 
treatment at the government hospital until he is too weak to earn 
bread, or until emaciation is present and cachexia is threatened. 
Of Sandwith's 162 hospital cases the average time they were ill be- 
fore entry was two years; in 36 there was illness of less than one 
year, and 9 were ill for five years and longer. Siler investigated 
the number of previous attacks among pellagrins in Illinois, and 
found of 104 cases 25 percent had suffered three previous attacks, 
52 percent two previous attacks, and 23 percent only one previous 
attack. My own cases in private practice average about three and 
one-half years. It is probable that the average length of the disease 
in Italy is between five and ten years, and in America and Egypt 
about five years. 

DURATION OF A SINGLE ATTACK. 

This ranges from the mild and often unnoticed attack in an 
infant, lasting a week, with an erythema hardly discernible, to the 
severe subchronic attack, which lasts from the initial onset to death, 
or from six months to two years. By an attack is included the 
premonitory symptoms, the dermatitis, with accompanying digestive 
disorders, and the gradual disappearance of the objective signs of 
the disease. The subsequent emaciation, weakness, and neuras- 
thenic condition are to be considered the results of the attack, rather 



86 



PELLAGRA. 



than a part of it. A single typical spring attack, lasting from 
six weeks to three months, consists of three essential elements: (1) 
onset of the attack, (2) the outbreak of the attack, (3) the reces- 
sion of the attack. A diagram will render the wisdom of division 
into these different periods clearly evident. The line a b does not 
coincide with the base line A B, indicating the lesions from the 
single attack. 

1. Onset. — This period includes the prodromal symptoms, which 
begin toward the latter part of the period of incubation, and corre- 
sponds to the preerythematous stage noted by many writers. Its 
duration varies, but, as a rule, five to thirty days are the limits, 
with a probable average of fifteen days, or from two to three weeks. 



Outbreak. 




4 



' c e Si 



H 



°U. 



-B 



Fig. 13. — Diagram showing periods in an attack. 



This period of onset may be altogether absent, and the dermatitis 
be the first symptom. Its severity is usually proportionate to the 
severity of the period of outbreak, and it, of course, closes with 
the advent of the outbreak. It is the period of minor symptoms, 
whose aggregate would lead both patient and doctor -to use the 
word "bilious" or "spring fever." There is lassitude, general 
malaise, slight mental and physical inertia, lack of appetite, 
epigastric uneasiness, bulimia, coated tongue, occasional relaxation 
of the bowels, and a systemic desire to rest. At this stage the 
tongue, though coated, may present red, slightly swollen and occa- 
sionally cyanosed papillae on the tip or edges, but no ulceration or 
buccal pain. It is a period of pathological introspection rather 
than of an objective disease. A burning sensation in the stomach, 
or on the hands or feet, is strikingly suspicious, and the occurrence 
of this group of symptoms in the spring in a patient in the country, 
especially if in an endemic pellagrous area, should make the physi- 
cian both silent and careful. 

2. Outbreak. — This period of outbreak closes the period of onset, 
and ushers in the objective symptoms that make pellagra so easy 
of diagnosis at this time of culmination of the single attack. The 
biliousness of the patient has become the pellagra of the physician. 



CLASSIFICATION. 



87 



The lassitude and malaise, the desire for rest and quiet, the mental 
and physical inertia, are now noises in the ears, vertigo, weakness 
in the lower extremities, occasional headache, increased reflexes, 
conversation is slow, the usual vivacity and force of the mind are 




Fig. 14. — Pellagra during period of attack. Typical wrist band, raw tongue, and erup- 
tion on face. (By Dr. O. C. Bass.) 



subdued and low, and depression has taken the place of the normal 
happiness of life. The backs of the hands are covered to a greater 
or less degree with a symmetrical dermatitis resembling a sunburn 
in the lighter attacks, and a sunburn with the tint of a full ripe 



88 PELLAGRA. 

plum in the more severe attacks. Above the redness and around 
the borders the skin is rough ; the elbows over the olecranon process 
are rough; there may be with this some roughness or dermatitis 
en parts of the face, neck, forehead, feet, and knees. There is an 
undue sensitiveness to sunlight or heat of any kind, slight pains 
in the abdomen occur, the pulse is faster, and fever is absent. The 
digestive symptoms of the onset are now really evident. The lips 
are red, the saliva is increased, and the tongue is smooth and of 
a beety nakedness ; the papillag are red and prominent, the tip and 
edges are raw in small areas; the soft palate, fauces, and throat 
are red and tender, and the esophagus seems in the same condi- 
tion. There is actual diarrhea, with a peculiar odor to the stools, 
a sense of nausea develops, gas increases in the intestines, and one 
is reminded of an acute gastroenteritis. The facial expression is 
one of anxiety, the neurasthenic element arrives, and it is evident 
that some flesh has been lost. The patient is suddenly and tem- 
porarily a neurasthenic, with accompanying cutaneous and gastro- 
intestinal symptoms. 

3. Recession. — The period of outbreak continues from one week 
to a month, and, as the symptoms that characterize it begin to 
lessen, the period of recession has begun. The patient feels bet- 
ter, pains disappear, and appetite returns. The buccal and lingual 
areas return to their natural state, except the covering of the 
tongue seems strangely slow and delayed. The throat heals, and 
acid foods can be swallowed without burning. The stomach feels 
natural, digestion improves, the number of stools decreases and 
again assume their normal consistency. The dermotagrous area 
desquamates, and the skin becomes smooth. The erythematous area 
on the back of the hands desquamates in larger scales, and a cleaner, 
lighter skin, slightly pigmented perhaps, appears beneath. The 
ends of the fingers seem unusually pink and clean, and the sensa- 
tions of burning depart. The face assumes its wonted brightness, 
and. cheerfulness takes the place of depression and sadness. The 
step again becomes elastic, and the sense of well-being and strength 
returns. The pellagrin thinks he is well. 

Pellagra, unlike a garment, is not made to pattern, and these 
symptoms are subject to great variation. These manifold symp- 
toms vary in their order, in number, in association, and in severity. 
The first symptom may be the dermatitis, and for the first few 
seasons it may be the only noticeable symptom. There may be a 



CLASSIFICATION. 89 

dermatitis and malaise, with entire absence of gastrointestinal 
symptoms. The skin may itch and burning sensation be absent. 
The attack may be so slight that it interferes with neither work, 
sleep, nor strength ; or so severe that the first attack is malignant 
pellagra and death comes quickly. The dermatitis, instead of dry, 
may be of an exudative type, with vesicles, rupture, and ulceration. 
Constipation may occur and diarrhea be absent even in the period 
of outbreak. The neurasthenic element may be absent, weight 
may remain as usual, and good spirits instead of depression be the 
rule. Appetite may continue as usual, or even be increased to 
greediness. Thirst may increase, or there may be a repugnance to 
water. Lassitude, dermatitis, and the tongue without a coat are 
the rule. 



ACUTE PELLAGRA. 

The idea involved in the phrase "acute pellagra" is threefold: 
(1) it includes a pellagrous attack which is severe in its symptoms 
and prostrating in its effect; (2) temporary, limited, and not 
chronic in time ; and ( 3 ) characterized by a fever, with extremes 
of 101 u to 105°. These three ideas of severity, brevity, and fever 
caused the unfortunate term "typhoid pellagra" to be applied to 
this acute pellagra. Typhoid fever is one disease, and pellagra 
is another disease, and the two rarely occur together in the same 
individual. Procopiu and "Watson each report two cases of typhoid 
in pellagrins, and even here it would be more correct to say that 
these pellagrins had typhoid fever complicating their pellagra, 
rather than to call the association of the two diseases typhoid pella- 
gra. In this acute pellagra as it occurs the bacillus typhosus is 
not present, and the disuse of the term typhoid would be a gain 
in the nomenclature of pellagra. 

The term "acute pellagra," as now applied to three conditions 
which occur, is (1) a primary acute attack of pellagra; (2) an 
acute attack in the course of the disease — sudden, severe, and 
febrile in its manifestation; (3) a terminal state of chronic pella- 
gra, with prostration, convulsive seizures, fever, diarrhea, and 
emaciation. It seems hardly consistent to call the terminal stage of 
a most chronic malady the acute form of the disease, and a similar 
inconsistency arises when acute pellagra develops in the course of 
the chronic form. To be consistent, acute should apply only to 



90 PELLAGRA. 

the primary attack, malignant in its nature. Pellagra is not noted 
for consistency, and acute pellagra includes all three conditions 
mentioned above. Each of the three is similar in symptoms and 
in duration, but each differs in the time in which it appears in 
the course of the disease. Classified according to time of appear- 
ance, they are as follows : 



Acute pellagra. 
Malignant pellagra. 



1. Primary acute pellagra, first attack. 

2. Secondary acute pellagra, developing suddenly in 

usual chronic form. 

3. Terminal acute pellagra, ending cachectic stage, and 

fatal. 



The duration of acute pellagra ranges from two weeks to three 
months; a duration of less than two weeks is extremely rare. It 
is sudden in onset, and the patient goes to bed at once. Prostra- 
tion seems out of proportion to the fever, and the pulse is high in 
proportion to the fever, wherein it differs notably from typhoid 
fever. Rarely is the pulse lower than 120, often it runs to 130, 
and higher as death approaches. The heart is not enlarged, and 
the sounds seem humdrum and low; the fever is continuous, with- 
out any regular morning and evening variations. The pulse is 
small, often irregular. Procopiu calls it a filiform pulse. The 
coat of the red tongue is gone, and fissures cover the dorsal surface, 
a true dissecting glossitis. Stomatitis, pharyngitis, gastroenteritis, 
and rectitis are usually present. A serous diarrhea, stubborn and 
persistent, is more frequent in the terminal acute type, with an 
accompanying emaciation, which ends cachexia and ushers in 
marasmus. 

Added to the difficulty in swallowing is dyspepsia, nausea, 
aversion to food and often to drink; prostration, loss of vital and 
muscular power, a fetid perspiration, and a peculiar pellagrous 
odor increase the general despair. The skin takes on a deeper hue, 
approaching lividity, and there may be the typical dermatitis and 
rough skin. Petechias may develop in the skin, bedsores on the 
supporting areas, trophic changes in the nails, wrinkled forehead, 
and rapid mummification. Instead of immobility and permanent 
dorsal decubitus, tetanic and meningeal symptoms arise, which are 
probably due to an advance of the pellagrous process in the cord 
and brain, with inflammation and exudate in some cases on the 
meninges and the cortex. Tremors, tetanic tossing to and fro, 



CLASSIFICATION. 91 

convulsions, opisthotonos, emprosthotonos, localized muscular con- 
tractions, delirium, mutterings, mania, depressive states, and hal- 
lucinosis mark the departure of the intellect. 

Toward the last, incontinence of urine and feces may develop. 
The urine is probably increased, excepting the rare cases with 
uremic symptoms. The specific gravity is low ; hyalin and granular 
casts, with occasional corpuscular elements, and albumen are often 
present. The course of the attack is rapid, death the rule, and 
temporary recovery the exception. Such a patient never recovers 
from pellagra, but recovery from the attack may grant a tem- 
porary respite. Terminal acute pellagra is always fatal. 

Differential diagnosis and post-morten findings will be found in 
appropriate sections. (See page 208.) 

SUBCHRONIC PELLAGRA. 

Convalescent Pellagra. 

This is the least serious of the forms of pellagra. In itself it is 
proof that a pellagrin may recover permanently from the disease 
and that treatment is really worth while. Fritz, at Inzago, called 
my attention to this type of the malady and to its evanescent 
tendency. In his thirty years' experience he had often observed 
children who developed pellagra to the extent of a mild dermatosis 
and dyspepsia, and after not more than two years of pellagrous 
symptoms, usually one year, recovered, grew into healthy men and 
women, and never afterward had any pellagrous symptoms what- 
soever. One of his patients, a boy, gained forty pounds in three 
months. This is true in Italy and in Roumania, and as the disease 
advances in America, and its different degrees of severity become 
more apparent, evidence will accumulate as to the convalescent 
form. Fritz 7 cases among the men married and raised large fami- 
lies, and that with no pellagra among their children or any stigmata 
of pellagra. The women married and bore children, often large 
families, and with no miscarriages. The boys, on reaching man- 
hood, stood the rigid physical examination, were often accepted as 
soldiers in the Italian army, and became strong men and good 
soldiers. Under this division come also many of the cases that 
Sandwith found when he examined 352 presumably healthy men 
and boys in eleven different villages in Egypt, and found 127 of 
them suffering with unmistakable signs of pellagra. 



92 PELLAGRA. 

Pellagra may be so mild that the pellagrin suffers no inconven- 
ience and is unaware of the presence of any disease whatsoever. 
Infants and young children develop the disease and present to the 
mother no signs of sickness, play and run as usual, and eat and 
sleep as well as ever. Pellagra varies as much in its severity as 
in its mass of symptoms, and one to see convalescent types of pella- 
gra has only to visit the various pellagrosari in Italy. In Amer- 
ica this subchronic type is extremely rare as compared with Italy, 
but, as time goes on, the extreme virulence of American pellagra 
will probably decrease with an increase in the number of cases of 
the convalescent type. 

Convalescent pellagra does not advance beyond the stage of ini- 
tiation. It is the pellagra of dyspepsia and dermatosis, with the 
practical absence of all the neurasthenic symptoms. It is well 
known that the initial stage may last in chronic pellagra for ten 
years, but in the present form even the initial stage is not far ad- 
vanced. The cause of pellagra fails to gain a foothold, its tendrils 
do not take root in the body soil, and after one or two vernal at- 
tempts it surrenders. Weight is the great mass symptom of pella- 
gra, and here there is no emaciation and often no loss in weight. 
The metabolic processes proceed as usual, appetite continues, sleep 
is good, and work is not interfered with. Young people are most 
often affected with this type, and their natural reserve force and 
resisting power help to ward off the disease. Youth is the best 
medicine in pellagra. 

The dermatitis is mild, rarely extends far above the wrist, comes 
quickly and goes quickly, leaving no objective change in the skin. 
The wet form never occurs in this type. The dermotagra is nearly 
always limited to the flexor surface of the forearm and to the elbow. 
The forehead may occasionally show a little branny roughness, 
but no dermatitis. The buccal mucosa is not very tender, though 
it is nearly always slightly red. The tongue does not have the 
entire nakedness, ulceration, and fissured glossitis of the more 
severe forms. It does not pain the patient to swallow, and diges- 
tion is rarely interfered with to any extent. For a day or two, 
rarely longer than a week to any extent, does diarrhea exist. The 
bowels are rather relaxed than loose, and constipation is often 
present; in many of this type no change occurs in the action of 
the alimentary canal of which the patient is aware. In two weeks 
to a month all signs of the disease are gone, and the health is as 



CLASSIFICATION. 93 

good as ever. There may be one or two recurrences, but of no 
greater moment than the first attack. Anemia is not pronounced, 
weakness is not felt, and recovery is without incident. 

Cachectic Form. 

Strambio must have had this type in mind when he spoke of 
continuous pellagra. It is true that cachectic pellagra does have 
periods of remission, but they are so slight M ^Mt both physician and 
patient feel that the disease is still actively ; . peent. There is. really 
no level in cachectic pellagra, and down-g Uj is the rule. There 
is no up-grade, because the patient does d til et better. The first 
attack is inordinately severe, even fever of hjj|( or less may be pres- 
ent, the pulse quickly rises to 100° and i ifcc, and the digestive 
symptoms are pronounced. The lips are red, often cracked and 
painful, and in one case I saw there was a continuous herpes on 
the lips. The tongue is red, with small ulcers on the tip and 
margins, and papillae are prominent, and the circumvallate papillae 
begin rising almost to the dignity of warts in their size and firm- 
ness. The soft palate, fauces, pharynx, and buccal mucosa are 
red, inflamed, and on the anterior pillars is occasionally a livid, 
cyanotic area which seems on the eve of ulceration. Indigestion, 
nausea, actual vomiting, diarrhea that is continuous, though not as 
severe as in the acute types, abdominal distention, gastralgia, and 
epigastric weights are so many separate blows on the general nutri- 
tion, and gradual loss of weight and emaciation introduce cachexia. 
After the first attack the patient is thin, cachectic, a profound 
neurasthenic, discouraged, mental activity gone, and despair and 
tears are moods in his neurasthenia. 

The essential difference in this form is the absence of any real 
period of intermission. The attack continues, and the loss of weight 
gradually increases. The dermatitis may disappear, leaving a pig- 
mented area in its trail. On careful examination the dermotagra 
remains on the elbows, flexor surface of the forearm, and even on 
the arms and shoulders, especially if in the primary attack the 
skin involvement had this area. The mouth rarely entirely heals, 
and, even if it appears well, in another week a new wave of in- 
flammation sweeps over the mucosa of the oral cavity. The tongue 
never resumes its normal coat and state; on its tip and margins 
are red areas, and the papillae are more or less prominent. Fre- 
quently the gums are red and tender, and toward the latter stages 



94 PELLAGRA. 

recede, with a collection of putrefactive material on the gum edges, 
giving the appearance of the mouth in Riggs' disease. As a rule, 
the abdomen is flat, and in one case of a woman of 34 a typical 
boat-shaped abdomen was present even in the periods of active 
diarrhea. There may be burning in the feet, occasional nights of 
insomnia, and the temperature may rise to 101°, with five to ten 
stools daily for a week, and dissolution appear near. The fever 
and diarrhea abate, sfd the former ability to sit up and even walk 
may return. After jure of the severe weeks the cachexia and gen- 
eral debility are mor , -Apparent, listlessness increases, the emotions 
come more to the sun ace, recurring attacks of erythema may de- 
velop, and the approa;' h. of death nears usually without pronounced 
symptoms of insanitj/' Sunken eyes, wasted face, keenly drawn 
fingers, and skin and bones represent what six to twenty-four 
months ago was a healthy, vigorous man or woman. I saw one 
case of this course in a girl of 8 years. At different times fever 
is present in this type, but not of the severity or length of the acute 
type. In women there is amenorrhea as a rule. 

It should be remembered that in a spring attack, with a cachexia 
resulting in midsummer, the recurrence in September or October 
of an autumn attack may close the scene, though occasionally the 
patient may last through the winter until the following spring or 
summer. Even in midwinter the evidences of the disease are still 
present on the tongue, hands, and gums, with weakness, emacia- 
tion, and neurasthenic cachexia. This rapid course of the disease 
is more common at the present time in America than in Italy, 
though I am convinced from a study of the literature that this 
cachectic type was also common in Italy about the close of the 
eighteenth century. This type is chronic pellagra, with the omis- 
sion of the stages of dyspepsia and neurasthenia, and with the 
early onset and rapid course of the stage of cachexia. 



CHRONIC PELLAGRA. 

Before one can understand pellagra he must have a general con- 
ception of the disease from its inception to its termination. It is 
a chronic disease, and, as time passes, the malady tends to progress. 
It is one thing to know pellagra at the acme of the spring attack, 
but it is another matter to comprehend the disease with its remis- 
sions and intermissions, its conglomeration of variations in season 






CLASSIFICATION. 95 

and out of season, and the fact that, once firmly fixed in the system, 
the periodic attacks are vernal links in the chain of a steady pro- 
gression toward cachexia, insanity, and death. Jansen, of Leyden, 
in his monograph on pellagra written in 1787, accents this idea in 
his definition: "An endemic disease usually manifesting itself 
first in the spring by rose-colored spots on the back of the hands, 
disappearing in winter, but which almost always recurs the follow- 
ing year full of more serious symptoms- at length attended by 
melancholia, mania, and convulsions; with exceptions here and 
there, it causes death." 

Jansen wrote his work in Latin,, and his description of the 
disease, splendid as it is, was improved by the excellent translation 
made by Chevalier, which appeared in the Tiondon Medical Review 
and Magazine in May, 1799. Chevalier's comments and transla- 
tion constitute the first article in the English language on pellagra. 
This article takes into account the progressive element in chronic 
pellagra, and from it as a basis the different stages of the chronic 
form become apparent. I give Jansen 's delineation of the clinical 
course in full, for I have found nowhere else in the literature so 
classic a description. 

About the month of March or April, when the season invites the farmers 
to cultivate their fields, it often happens that a shining red spot suddenly 
arises on the back of the hand, resembling the common erysipelas, but without 
much itching or pain, or indeed any other particular inconvenience. Both 
men and women, boys and girls, are equally subject to it. Sometimes this 
spot affects both hands, without appearing on any other part of the body; 
not uncommonly it arises also on the shins, sometimes on the neck, and now 
and then, though very rarely, on the face. It is also sometimes seen on the 
breasts of women where they are not covered by the clothes, but such parts 
of the body as are not exposed to the air are seldom affected, nor has it ever 
been observed to attack the palm of the hand or the sole of the foot. 

This red spot elevates the skin a little, producing numerous small tubercles 
of different colors; the skin becomes dry and cracks, and the epidermis some- 
times assumes a fibrous appearance. At length it falls off in white furfu- 
raceous scales, but the shining redness underneath still continues, and in some 
instances remains through the following winter. In the meantime, except- 
ing this mere local affection, the health is not the least impaired; the patient 
performs all his rural labors as before, enjoys a good appetite, eats heartily, 
and digests well. The bowels are generally relaxed at the very commencement 
of the disease, and continue so throughout its whole course. All the other 
excretions are as usual, and in females the menses return at their accustomed 
periods and in the proper quantity. 

But what is most surprising is that in the month of September, when the 



96 PELLAGRA. 

heat of summer is over — in some cases sooner, in others later — the disorder 
generally altogether disappears, and the skin resumes its natural, healthy 
appearance. This change has been known to take place as early as the latter 
end of May or June when it has been only in its earliest stage. The patients, 
however, are not now to be considered as well; the disease hides itself, but is 
not eradicated. For no sooner does the following spring return, but it quickly 
reappears and generally is accompanied with severer symptoms. The spot 
grows larger, the skin becomes more unequal and hard, with deeper cracks. 
The patient now begins to feel uneasiness in the head, becomes fearful, dull, 
less capable of labor, and much wearied with his usual exertions. He is 
exceedingly affected by the change in the atmosphere, and impatient both of 
cold and heat. Nevertheless, he generally gets through his ordinary labor, 
with less vigor and cheerfulness indeed than formerly, but still without being- 
obliged to take his bed; and he has no fever, his appetite continues good, 
and the chylopoietic viscera perforin their proper functions. When the pel- 
lagra has arrived even at this stage, the returning winter nevertheless com- 
monly restores the patient to apparent health ; but the more severe the symp- 
toms have been, and the deeper root the disease has taken, the more certainly 
does the return of spring reproduce it, with additional violence. Sometimes 
the disease in the skin disappears, but the other symptoms remain notwith- 
standing. 

The powers of both the mind and body now become daily more enfeebled; 
feverishness, watchings, vertigo, and at length complete melancholy super- 
vene. Nor is there a more distressing melancholy anywhere to be seen than 
takes place in this disease. On entering the hospital at Legnano I was aston- 
ished at the mournful spectacle I beheld, especially in the women's ward. 
There they all sat, indolent, languid, and with downcast looks, their eyes 
expressing distress, weeping without cause, and scarcely returning an answer 
when spoken to; so that a person would suppose himself to be among fools 
and mad people, and indeed with very good reason, for gradually this melan- 
choly increases and at length ends in real mania. Many, as I had opportunity 
of observing in this hospital, were covered with a peculiar and characteristic 
sweat, having a very offensive smell, which I know not how better to express 
than by comparing it to the smell of moldy bread. A person accustomed to 
see the disease would at once recognize it by this single symptom. Many 
complained of a burning pain at night in the soles of their feet, which often 
deprived them of sleep. Some are affected with double vision, others with 
dementia, others with visceral obstructions, others with additional symptoms. 
Nevertheless, fever still keeps off, the appetite is unimpaired, and the secre- 
tions are regularly carried on. 

But the disease goes on increasing, the nerves are more debilitated, the 
legs and thighs lose the power of motion, stupor or delirium comes on, and 
the melancholy terminates in confirmed mania. In the hospital at Legnano 
I saw both men and women in this maniacal state. Some lay quiet, others 
were raving and obliged to be tied down to the bed to prevent them from 
doing mischief to themselves or others. In almost all these the pulse was 
small, slow, and without any character of fever. One woman appeared to 
have a slight degree of furor uterinus, for at the sight of men she became 



CLASSIFICATION. 



97 



merry, smiled, offered kisses, and by her gestures desired them to come 
toward her. Some were occupied in constant prayers, some pleased them- 
selves with laughter, and others with other things. But it was remarkable, 
as Moscati observed, that all who were in this stage of the disease had a 
strong propensity to drown themselves. They now begin to grow emaciated, 
and the delirium is often followed by a species of tabes. A colliquative diar- 
rhea comes on, which no remedy can stop, as has also been observed in nos- 
talgia. Sometimes in pellagra the diarrhea comes on before the delirium, and 
the delirium and stupor mutually interchange with each other. The appetite 
often suddenly fails, so that the sick will sometimes go for nearly a week 
without tasting food. Not uncommonly it returns as suddenly, so that they 
eagerly devour whatever is offered them, and this even at times when they 
are horribly convulsed. The convulsions with which they are attacked are 
most shocking to see, and are of almost every kind; catalepsy is frequent, 
which has been described by writers. I saw one girl in bed who was violently 
distorted by opisthotonos every time she attempted to rise; some are seized 
with emprosthotonos, and others with other species of tetanus. At length 
syncope and death close the tragedy, often without any symptom of fever 
occurring throughout the whole course of the disease. 

STAGES OF CHRONIC PELLAGRA. 

The course of chronic pellagra can best be represented and under- 
stood by a diagram, with the dermatosis as the common basis, 
since it is common to all three stages and is the one objective symp- 
tom that connects the varying pictures of dyspepsia, neurasthenia, 
and cachexia. 

Dermatosis of Pellagra. 



Degree of 
initiation. 




2. ; 


< 3. 


Degree of \ 


J Degree of 


confirmation. ( 


J desperation 




Stage of dyspepsia — Stage of neurasthenia — Stage of cachexia. 



The Dermatosis of Pellagra. 
(a) Dermatitis or erythema; (b) dermotagra or rough skin. 

Fig. 15. — Diagram showing stages of chronic pellagra with relation to clinical symptoms, 

The time of a single pellagrous attack was divided into period 
of onset, outbreak, and recession, while the course of chronic pella- 



98 PELLAGRA. 

gra includes a far greater length of time divided into relatively 
long stages. Periods in the single attack are to be distinguished 
from stages in the chronic course ; the period refers to a short time 
and the stage to long duration, involving the idea of continuance. 
To a certain extent these stages are as abitrary in their separation 
and limitation as are the three periods in the recurrent single 
attack. Each stage in chronic pellagra consists of recurrent at- 
tacks of activity and times of intermission, or inactivity of the 
pellagrous advance. The node of the jointed reed represents the 
attack in the spring, and the internode the intermission between 
attacks. The internode is longer than the node, and the inter- 
mission longer than the attack. To carry the figure further, the 
ten-foot cane is divided into proximal, middle, and distal parts, 
each in turn formed of several nodes and internodes. Chronic 
pellagra is divided into degrees of initiation corresponding to the 
clinical stage of dyspepsia, the degree of confirmation correspond- 
ing to the clinical stage of neurasthenia, the degree of desperation 
corresponding to the clinical stage of cachexia, and each of these 
three degrees or stages consists of periodic attacks and interperiodic 
intermissions. 

To use Cabot's phrase, the presenting symptom in the initial 
stage is dyspepsia, the presenting symptom in the confirmed stage 
is neurasthenia, and the presenting symptom in the desperate con- 
dition of the late chronic pellagra is cachexia. These stages lap 
like shingles on a roof, and, while it is no great matter for the 
physician to tell which stage confronts him in the pellagrin, it is 
altogether difficult to know when and where one ends and the next 
stage begins. The fundamental idea in chronic pellagra is progres- 
sion, and these stages are epochs in this progress. It is natural 
that they should vary very much in time, but as a rule the duration 
decreases from first to last ; the dyspeptic stage may last for fifteen 
years, and then be short of its full development. 

A symptom that is temporary in one stage may become permanent 
in the next and of increasing intensity. Temporary neurasthenia 
often appears in the attack of the first stage, but permanent neuras- 
thenia is the marked symptom of the confirmed degree. Diarrhea 
is temporary in the dyspeptic time, longer in the neurasthenic 
stage, and practically continuous in the shorter cachectic forms. 
Emaciation presents itself in the attacks during the second stage, 
but there is usually a gain in weight in the intermission following ; 



CLASSIFICATION. 99 

emaciation is, however, constant in the cachectic time and of dis- 
tressing permanency. In America these facts are not so evident 
because here the disease is as yet more strikingly temporary in 
time and severe in its aggregate symptoms, and therefore the pre- 
senting symptoms of the different stages and the evolution of a 
symptom through the course of the disease is less apparent. Never- 
theless, each stage of chronic pellagra is an aggregate of more or 
less well-defined symptoms, and the course of the disease progresses 
by the evolution and increasing intensity of these symptoms. 

The initial stage marks the beginning of the disease, and years 
may elapse before the disease gains appreciable foothold. Several 
years may elapse without an attack, and then suddenly a more 
severe attack develops, with the subsequent appearance of the neu- 
rasthenic stage. Indeed, the confirmed degree may be less serious 
than the initial degree, and the feebleness of the supposed on- 
coming cachexia never develop. Instead of progressive seriousness, 
there may occur a progressive lessening of the symptoms. The 
symptoms of the first and second stages may occur at the same 
time, and, as very frequently happens, the second and third stages 
seem to be identical. In this country the initial stage and simple 
dyspepsia in many cases fail to appear, and the first spring attack 
ushers the pellagrin into a state of confirmed neurasthenia. 

In older pellagrins one is often called upon to distinguish differ- 
ent diseases and their effects from a superimposed pellagra with 
its inroads, and, while the diagnosis of the different diseases may 
be easy, the relative effects are difficult. The following case illus- 
trates this: 

A white man, 58 years old, developed in 1909 a severe attack of 
articular rheumatism. He was in bed for three months and re- 
covered from the attack, but with hypertrophic arthritis in both 
ankles. He had been a farmer, but, on account of his feebleness, 
went to work in a cotton mill in a small town. In August of 
1911 he developed a typical pellagra, with dyspepsia, dermatitis, 
but practically no dermotagra. I saw him in November, and, from 
his description of his pellagrous attack and present symptoms, I 
judged the attack was mild and initial in degree. He was a 
neurasthenic of a most confirmed type, his heart sounds were weak, 
and a blowing mitral alternated with a loud aortic regurgitant. 
He had evidently suffered with a late endocarditis of rheumatic 
origin from the weakness and evident roughness of all the valvular 



100 PELLAGRA. 

sounds. Severe arteriosclerosis was present, and his urine showed 
hyalin and granular casts, with a large amount of indican. The 
evolution, in order, was probably arteriosclerosis, aortic insuffi- 
ciency, Brightism, rheumatism with chronic arthritis, endocarditis, 
and pellagra over it all. He looked as if cachexia was imminent, 
and yet the pellagrous attack was mild, and it would be impos- 
sible to state accurately the part pellagra played in causing his 
condition, or to what degree the pellagra had attained. According 
to him, this was the first attack, but earlier attacks may have been 
so slight that they were not noticed, or the lowered vitality fol- 
lowing rheumatism and endocarditis may have floated a latent pel- 
lagra. 

1. Initial Degree — Stage of Dyspepsia. — Duration, from one to 
twenty years. It consists of one or two attacks in the year ; usually 
the spring attack is persistent, and the autumn attack is not con- 
stant. With two yearly attacks, the progress of the disease is 
faster, and the duration of this stage shorter. The attack has 
been described, but in this stage it tends to be mild, and may 
last but a week, and averages from four to six weeks. It may be 
so mild as to pass unnoticed, and this may occur several years 
in succession before it is severe enough to arouse the suspicion of 
the patient. The dermatitis in the first few years may be con- 
sidered a sunburn, especially in those cases in which the general 
health is unimpaired, and the usual work and play are not inter- 
fered with. The appetite is good, except in the height of the at- 
tack in the marked cases. In the majority of pellagrins the bowels 
tend to relaxation, more during the attack and less in the inter- 
mission, but constipation occurs, and often the bowels may be 
normal throughout the early part of this state. Dyspepsia, bulimia, 
gas in the intestines, are usually present at various times, and 
especially during the beginning of the spring attack. The dys- 
pepsia is apt to be more noticed than the dermatitis. Belching 
occurs, the pellagra tongue as heretofore described, occasional 
abdominal pain, and perhaps weakness and vertigo, especially in 
the attack. After the attack and during the fall and winter the 
skin is frequently apparently normal, and often one is unable, 
except on very close observation, to note any evidence that the 
dermatitis has ever been present. At times, and more frequently 
after several attacks, the dermatitis area is slightly darker and 
more pigmented than normal, and the elbows a little rough. 



CLASSIFICATION. 101 

Weight may continue as usual, with the loss of a few pounds 
during the annual attack, which, however, is quickly regained. 
During the summer, fall, and winter, with the absence of the au- 
tumnal recurrence, health and spirits are good, and the spring 
malaise considered natural and to be expected as peculiar to the 
patient's constitution. At one time of the year the patient feels 
bad, but he may think this is due to spring and not to disease. 
Toward the close of this stage, in America from three to five years 
as a rule, symptoms of neurasthenia begin to creep in, less work 
is done, headache comes, the spirits lack buoyancy, and the walk 
is not so rapid and elastic. Mental activity lessens, and the mild 
malady of the first stage begins to be succeeded by the more con- 
firmed degree of the neurasthenic time. 

2. Confirmed Degree — Stage of Neurasthenia. — Duration, from 
one to ten years ; in America usually less than five years. The 
attacks of this stage differ from those of the dyspeptic stage, in 
degree rather than in quality, and in the aggravation of the 
symptoms of the first rather than the introduction of new symp- 
toms. The attacks are certainly more severe, last longer, recovery 
from them is slower, and their permanent results strike deeper 
into the mental and physical strength. In the language of Mayr 
in Hebra's Treatise, "the fresh symptoms which now present 
themselves do not concern the eruption, but rather indicate the 
progress of the internal malady." The cutaneous involvement 
pursues a beaten track throughout the course of chronic pellagra, 
while the new symptoms refer to the greater involvement of the 
nervous system and the appearance of symptoms which are signs 
of this new and more serious turn of the disease. Here one is 
tempted to ask what part of the new symptoms is due to organic 
changes in the nervous system and what part to the aggravation 
of the condition of the alimentary tract and the resulting effect 
on the general nutrition. The great difference in the two stages 
is not in the attacks in the spring or fall, but in the marked differ- 
ence in the pellagrin between the attacks. In the intermission of 
the dyspeptic stage he is apparently and practically well; in the 
second stage he is a confirmed neurasthenic all the time, and his 
normal metabolism begins to waver. The attack is more severe, 
and in the intermission he is more feeble. 

Loss of flesh is permanent, the forehead becomes wrinkled, the 
senile face is in evidence, the body is bent, and the walk is aged; 



102 PELLAGRA. 

he leans on a stick; at times he staggers and his legs are drank. 
"Weakness of the muscles is evident, fatigue comes after little exer- 
tion, and between attacks the condition of the pellagrin reminds 
one of Beard's description of a neurasthenic in his "Nervous Ex- 
haustion:" "Unwonted and unaccustomed muscular exercise is 
especially irksome to neurasthenic sufferers. They can do very 
well in an ordinary routine, but stepping out of this routine, and 
attempting something new to them, they quickly become wearied. 
The very narrow margin of muscular force is soon exhausted. 
This applies to both nervous and muscular exhaustion." Later 
in this stage develop tremor, cramps, contractures, cataleptic and 
epileptic states, tetanic movements, tendencies to fall in all direc- 
tions, uncertainty in all things. 

The tongue in the attacks is more inflamed, stomatitis more se- 
vere, even for a few days it may interfere with swallowing ; nausea, 
pyrosia, intense bulimia, real gastralgia, recurrent epigastric pain 
that brings the gastric crises of tabes to mind ; drooling saliva 
during the attack and occasionally during the intermission; in- 
creased number of stools during the attack, with a moldy odor; 
abdominal distention increased after eating, voracious appetite or 
refusal of food; a diarrhea that alternates with a constipation, 
or that continues intermittently, or even persistent constipation, 
tenesmus, gastritis, enteritis, and rectitis that vary in severity 
and in persistency. Both Strambio and Roussel considered the 
sudden attacks of diarrhea or vomiting that occur at this stage 
to be due to spasmodic phenomena arising from the nervous 
system. 

The pulse is more rapid, running often in the intermissions from 
80 to 100; dyspnea may develop, and occasionally slight dropsy, 
though these are not common in America. The reflexes are 
usually permanently exaggerated, vertigo, headache, heavy-headed- 
ness, drawing feelings in the back of the neck, pain in the back to 
one or the other side of the dorsal spine, and all or any of these 
absent at times ; and, like a neurasthenic, a sense of well-being and 
health alternates with nerve exhaustion and all the symptoms of 
the nervous dyspeptic. The mind loses its cunning ; no more is it the 
active human mind. Little tasks become like mountains, and the 
pellagrin is more content to sit and rest than to walk and work. 
Like Napoleon in his last days, he prefers rest to all the thrones 
of Europe. 



CLASSIFICATION. 103 

The hand is now no longer a normal hand. Even in the inter- 
missions its back is pigmented, the wrists are dark with a brownish- 
red color, and occasionally it has rounded to the front; the elbows 
are rough and the skin over them becomes thick; the knees are 
rough likewise, and even the feet and shins are sometimes darker 
than normal. Areas of dermatosis of the face or neck are now 
unusually dry and branny, and one often involuntarily thinks of 
dry, scaly eczema. The finger and toe tips seem pink and clean; 
the face rather reddish like a faint blush, or of a darker bronze 
like that of a bronzed diabetic. One man had this red hue over 
his back and between the anal folds. The hands, legs, and feet 
burn at times to despair, itching may alternate with burning, and 
the physician is asked to ' ' give a remedy that will stop this burning 
and let me sleep." The skin over the hands cracks, and is loose 
and wrinkled like the senile skin. The recurrent dermatitis has 
left an old man's hand. 

The urine is usually acid; the specific gravity may be normal, 
but is often lowered, and, according to Procopiu, gives in some 
cases the diazo reaction. The amount of urine is increased, with 
occasional traces of albuminuria and a few casts. Sight begins to 
fail, and reading is troublesome to the eyes and burdensome to 
the mind. The neurasthenic is naturally a sad person, and de- 
spondency, fear of water or attraction to it, desire to suicide, days 
of melancholia and despair, mark the wane of the mind, oncoming 
cachexia, and insanity. 

3. Degree of Desperation — Stage of Cachexia. — Duration, from 
one to five years, usually short. Dermatosis and dyspepsia char- 
acterize the initial time; dermatosis, indigestion, neurasthenia, and 
feebleness the confirmed time, and all these, with prostration, 
cachexia, and insanity added, occur in the degree of desperation. 
Death may occur early, or insanity develop and the pellagrin, 
with his pellagrous insanity and some cachectic symptoms, live 
many years. It is well to understand that pellagrous insanity 
may occur in the neurasthenic stage as well as in the last stage. 
Insanity in pellagra may come at any time. To walk through 
any asylum for the insane in the southern states and see the pel- 
lagrins is ample proof of this. At Mombello, in Italy, I saw two 
pellagrins with manic-depressive insanity, who weighed probably 
160 pounds each, were well and strong physically, and yet whose 
minds were gone in the initial stage. Dr. Green showed me at the 



104 PELLAGRA. 

Georgia asylum a negro of this type, who looked well nourished 
enough to do a day's work. 

Invalidism is the rule here. Paralysis, paraplegia, and hemi- 
plegia occur, though anesthetic areas are rare. Ankle clonus and 
the Babinski reflex may be present, and absence or presence of 
knee jerks. The delirium and diarrhea may alternate. 

Diarrhea may become blood-streaked, mucus is found in the 
stools, and a serous diarrhea, unyielding to any treatment, end 
in death. The hands are exceedingly thin, petechias may occur, 
and discolored spots as if the flesh had been bruised; the muscles 
atrophy and the subcutaneous fat is gone. Bed sores may develop, 
there is incontinence of feces and urine, and the gradual onset of 
acute terminal pellagra, with high fever and death. The discussion 
of pellagrous insanity will be found in the chapter on "Nervous 
System," page 171. 

PELLAGRA SINE EXANTHEMATA. 

I have in this month seen the patient described as Case 1, on 
page 18. The skin symptoms were absent, and only a long expe- 
rience with pellagrins would permit one to suspect a past pellagrous 
dermatosis. The pellagra tongue was present and occasional diar- 
rhea, Strambio believed that the skin symptoms could be absent 
during the entire course of chronic pellagra, including even in the 
spring attack, and to this condition Strambio gave the name of 
pellagra sine pellagra. He applied this phrase to the permanent 
absence of skin symptoms in pellagra, and not to the temporary 
absence during the annual intermission following the annual at- 
tack. Girelli, of Brescia, cited a case with violent pellagrous 
symptoms of twenty years' standing and no dermatosis. Roussel 
cites two cases. 

The phrase is misleading, and, literally translated, is "pellagra 
without pellagra." I have substituted for this a plainer phrase, 
and one that means just what it is intended to mean — pellagra 
sine exanthemata, or pellagra without the exanthem. Strambio 's 
phrase means pellagra without pellagra, whereas he meant that a 
marked pellagra does exist, but no skin involvement. It is prob- 
able that this condition does exist, but that it is very rare. The 
exanthem is coincident with the attack, as the erythema of scarlet 
fever is coincident with its attack; the pellagrous exanthem marks 



CLASSIFICATION. 105 

the exacerbation time of pellagra, and in this time it can certainly 
be absent and the internal malady be present. It is probable that 
a more careful study of the skin will show a pellagrous dermotagra 
in these cases, with absence of the dermatitis. A sharp distinc- 
tion is to be drawn between these, for in the past the attention 
has been focused nearly altogether on the dermatitis. I have under 
observation at this time a female pellagrin who, I know, has pel- 
lagra, and yet there has never been a dermatitis, but a noticeable 
dermotagra exists in the region of the elbows, on the flexor sur- 
face of the forearm, and at variable times on the back of the 
hands. When her tongue and diarrhea grow worse, the dermo- 
tagra increases. Harris describes three cases of pellagra sine ex- 
anthemata in the American Journal of the Medical Sciences for 
May, 1911. One should be very careful, and hesitate a long time 
before he makes a diagnosis of this form. I would prefer to ob- 
serve such a patient several months before reaching a conclusion 
in my own mind. In the meantime treatment for pellagra could 
be instituted if the pellagrous evidence was weighty. 

PSEUDO-PELLAGRA. 

It was an unfortunate day when Roussel applied the term 
pseudo-pellagra to pellagra. There is no pseudo-pellagra. Real 
pellagra is hard enough for a patient to suffer and for the phy- 
sician to treat, and the use of pseudo in regard to the disease is 
unwise. A disease is either pellagra or it is not pellagra, and 
there is no middle ground. Pseudo-pellagra is not pellagra; it i> 
some other disease. Pellagra is pellagra, and there is nothing false 
about it. Roussel applied the term more in derision of imagined 
and arbitrarily constructed groups of symptoms, which he called 
unites factices, in patients not pellagrous. Billod believed in 
pseudo-pellagra, and executed many marked diagnostic flounders ; 
Hardy confused pellagra and alcoholism; sporadic pellagra was 
unexplained and called pseudo-pellagra ; pellagrins who had never 
eaten corn in any form, but who had pellagra, were called pseudo- 
pellagrins. Because a confirmed alcoholic has a few nerve or di- 
gestive symptoms that pellagrins have is no reason to call him a 
pseudo-pellagrin. "When pellagra invades a country for the first 
time, inexperience on the part of some and fear on the part of 
others inclines to confusion in a few cases as to just what does 



106 PELLAGRA. 

constitute the pellagrous syndrome, and occasionally the diagnosis 
of pellagra is made without evidence and incorrectly. Referring 
to these conditions in France and the different maladies called 
pellagra and pseudo-pellagra, De Jeanne wrote: " These are mala- 
dies differing widely among themselves, and all of them differing 
widely from endemic pellagra, not only in the etiology, but also 
in the nature and concatenation of the symptoms." 



CHAPTER IV. 
THE ALIMENTARY TRACT IN PELLAGRA. 

In Edmond About 's novel, "Maitre Pierre," whose scenes are 
laid in the Landes in France, and which was published in 1844, 
the heroine says of pellagra: "It commences in the stomach and 
soon reaches the surface like a noxious weed which nourishes rankly 
everywhere." When the cause of pellagra is fully known, the 
reason for the extensive involvement of the gastrointestinal tract 
will become evident. As a rule, the symptoms that arise here are 
the earliest, the most persistent, and the most dangerous of all 
the pellagrous symptoms ; and of these pellagrous symptoms, diar- 
rhea holds the red flag, and reminds one of Lauder Brunton's 
statement that "diarrhea destroys more lives than any other dis- 
ease." The two great causes of gastrointestinal irritation are (1) 
those which concern the food and (2) those which concern the 
organism, and in the latter class pellagra is found. I am disposed 
to believe that for some reason the gastrointestinal tract should 
blame the nervous system for much of its condition in pellagra. 
Goodhart, quoted by Allbutt, writes : " It is no great exaggeration 
to say that there are only two forms of indigestion — that produced 
by overeating and drinking, and that due to a failure of the 
nervous power." The nervous power fails, and the gastrointes- 
tinal condition keeps pace with this failure.. 

These symptoms involve the oral cavity — always the tongue, the 
pharynx, the esophagus, the stomach, the large and small intestines, 
the salivary glands, the liver, pancreas, and spleen. There are 
organic and functional changes, and both to a marked degree. 
Stomatitis, ptyalism, glossitis, pharyngitis, esophagitis, gastritis and 
dyspepsia, enteritis and ulceration are in one sense the different 
and separate diseases whose union with variations present the ex- 
tensive pathology of the digestive system. With a few slight 
changes, Lauder Brunton's description of dyspepsia applies to the 
mass of symptoms of indigestion in pellagra : i l Briefly, the symp- 
toms of dyspepsia are a furred tongue, a bad taste in the mouth, 

107 



108 PELLAGRA. 

want of appetite or even loathing of food, vomiting, oppression in 
the chest, weight at the epigastrium, pain, distention, flatulence, 
acidity, eructations, pyrosis, constipation or diarrhea." 

THE TONGUE. 

The condition of the tongue is the most constant and most im- 
portant diagnostic symptom furnished by the digestive system. 
During the onset of the attack it is furred and coated, and the 
patient has occasional anorexia and bad breath. As the outbreak 
occurs, the lingual epithelium is lost, the tongue becomes red, is 
slightly swollen, and the tip and anterior lateral margins are first 
affected and then the back. Irregular fissures form in the middle 
and on the lateral margins; these sometimes cross the tongue and 
descend the sides like the outline of a cross section of an empty 
shoe box turned upside down. This stage is a dissecting glossitis. 
The true pellagra tongue is a tongue without a coat, the beet tongue 
— the "bald" tongue of Sandwith. Aphthous ulcers may develop 
on the tip and margins, and their rawness causes pain in eating. 
As the attack recedes, the tongue for a long period may present 
a few red papillae scattered over the tip, and the epithelium may 
never return with its characteristic thickness. 

This redness of the tongue is due to inflammation, and for a 
time after the attack the tongue may present a paleness due to 
anemia. This pallor is out of all proportion to the previous red- 
ness and fissured condition. The tongue improves as the attack 
recedes and inflames as the attack approaches, reaching the greatest 
inflammation at the acme of the outbreak. In the severe cases it 
is often tremulous, usually thick and beefy, and occasionally 
pointed. Occasionally the papillae may be dark at their tips, due 
probably to swelling with cyanosis. Sandwith 's 163 cases had tip 
and edges naked and red in one-half the number, one-fourth com- 
pletely denuded of epithelium, and only 5 had a coated tongue; 
37 were normal except for anemic pallor. Of 121 patients with 
tongue either completely or partially denuded on leaving hospital, 
45 returned as normal, and 38 remained partially denuded. As 
a rule, during the onset the tongue is coated, then gradually loses 
its coat, and the papillae at tip appear red and prominent; during 
the outbreak the tongue is red, fissured, and its coat gradually 
reappears as the attack recedes. During the periods of interims- 



ALIMENTARY TRACT IN PELLAGRA. 109 

sion the tongue may be strangely clean, unless one thinks of pel- 
lagra. It is well to remember that after surgical procedures in 
septic cases the tongue may be naked, red, and swollen, with ac- 
companying stomatitis; and in uremia the tip of the tongue may 
be similar to the pellagrous tongue. Acute alcoholism presents the 
inflamed tip, prominent papilhe, and tender margins. 

GUMS, TEETH, BUCCAL MUCOSA, PALATE. 

Between attacks the gums are usually normal, but during the 
outbreak the gums are inflamed in common with the rest of the 
oral mucosa. They are tender, often spongy and easy to bleed, 
as in scurvy; around the lower incisors this condition is most 
noticeable. The teeth are not affected, and in one series out of 
166 pellagrins 120 had sound teeth. Pellagrins usually can mas- 
ticate well, and with them the teeth do not in any way influence 
the gastrointestinal condition. The poison arises within in pel- 
lagra. 

Between the attacks, except in the subchronic cachectic form 
where there is no real intermission, the buccal mucosa is usually 
normal. During the outbreak stomatitis is present, and reaches 
its acme at the culmination of the dermatitis and the glossitis. 
At this time the outer border of the lips are dry, and, in the 
severe cases, of a cyanotic hue ; the inner border of the lips and 
cheeks are red, tender, raw, and swollen, and this inflammation 
extends over the buccal mucosa to such an extent that eating and 
swallowing are difficult, and even weak acid drinks are so painful 
and burning that they can not be taken. Occasionally Stenson's 
duct opens into a pit, instead of on the surface, on account of the 
swollen mucosa. Aphthous ulcers are common, and occasionally 
small blisters arise on the inside of the cheeks, which, when burst, 
leave the membrane dead and pale. These small bulla? are espe- 
cially noticeable as the period of recession begins. At this time 
the mucosa exfoliates, and is thrown off in macerated strands. In 
the very mild attacks the mucosa is only red and may be tender 
for a few days, but it lacks the velvety rawness of the severe 
forms. 

The latter half of the palate, including the uvula, the anterior 
and posterior pillars of the fauces, may be either red in the lighter 
attacks, inflamed on the anterior pillars, with scattered pin-point 



110 PELLAGRA. 

areas in the more severe attacks, and entirely raw, very red, and 
even ulcerated on the anterior pillars in the severe forms. The 
uvula may become edematous, sag, and add to the general pharyn- 
geal discomfort. Posteriorly the inflammation is neither as severe 
nor as uniform as anteriorly in the region of the labial frenum. 
Evidences of the oncoming stomatitis are first found anteriorly 
around the frenum, and it persists longer there. The actual 
stomatitis does not last longer than two weeks as a rule, and may 
cause inconvenience for only two or three days. As the attack 
recedes, the increased saliva decreases, the edema departs, the 
epithelial coverings regenerate, and the mouth feels and appears 
normal. 

SALIVARY GLANDS. 

Ptyalism is a variable symptom, depending on the degree of 
stomatitis present, and on an unknown factor in that a few cases 
present during the attack an almost continuous drooling of saliva 
from the mouth and an increased expectoration in the intermis- 
sions. One old lady of 60 years had a constant flow of saliva for 
three weeks, and then, when up and feeling well, stomatitis gone, 
she would have to spit about every fifteen minutes during her 
waking hours. Just why this extraordinary symptom should con- 
tinue I do not know. The increase synchronous with the stomatitis 
is primarily a reflex stimulation of the salivary and mucous glands, 
but it is also influenced by the hyperemia, degeneration, and in- 
flammation of the buccal mucosa. There is another factor than 
the stomatitis, because many pellagrins with severe stomatitis have 
only a small temporary increase in the saliva. There is present 
in these cases an abnormal chemical reaction of some kind, as 
proved by the fact that the saliva may be acid instead of alkaline. 
Taste may be disagreeable, and even salty or briny, giving rise 
to the Italian synonym of pellagra salso and umor salso, or salti- 
ness and salty phlegm. I saw one patient who had a drooling 
saliva for more than a month, and who died from exhaustion. 
Swint and Echols at Milledgeville showed me two female pellagrins, 
insane, dementia precox type, who were up and walking around 
with a constant production of thick, ropy strands of saliva flowing 
to such an extent that their garments were wet all the time. It 
has seemed that in those cases where the saliva was markedly in- 



ALIMENTARY TRACT IX PELLAGRA. Ill 

creased the diarrhea was less, and with decreased saliva there was 
an increase in the severity of the diarrhea. It seems that the 
body in pellagra is trying to get rid of something, and either 
diarrhea or salivation may remove it. 

Sandwith fonnd 6 out of 151 cases with a bilateral enlargement 
of the parotid gland. It occurs in children with the bald tongne, 
and dermatosis on face, ears, and neck. The parotitis is painless, 
and, like mumps, does not proceed to suppuration. "With the 
dermatitis at its height on the hands, the epitrochlear glands may 
become enlarged; and with the cutaneous involvement on the face 
and neck, through the lymphatics, the parotid gland may similarly 
enlarge. Certainly a far different process is present, because in 
mumps there is a tendency to a decrease in the saliva. The pel- 
lagrous saliva, increased in amount, is deficient in solids, and con- 
tains microscopically enormous numbers of enlarged flat epithelial 
cells, with debris from the tongue, teeth, and buccal mucosa. The 
parotid gland in the sheep secretes saliva continually, and a similar 
ability is certainly present in a few pellagrins, leading to the belief 
that the pellagrous toxin must influence the salivary center in the 
medulla, as all three pairs of salivary glands are affected. 

PHARYNGITIS AND ESOPHAGITIS. 

Inflammation of the pharnyx and esophagus is simply a con- 
tinuation of the pellagrous process. As the stomatitis grows worse, 
the sensation of rawness in the throat and esophagus increases, and 
also the pain in swallowing. I have seen a female pellagrin at- 
tempt to drink an orange albumen and complain that "it burns 
all the way down." The esophagitis can not be caused by the 
condition of the gastric juice, because the acidity is decreased and 
gastric regurgitation would therefore play no part. The throat 
and esophagus grow worse as the stomatitis increases, and better 
as the stomatitis improves. These symptoms exist only during 
the attack, and cause inconvenience chiefly during the period of 
outbreak. During recession, regeneration and healing of the 
mucosa is rapid. 

STOMACH AND INTESTINES. 

In these organs arise such symptoms as gastralgia, epigastric 
pain, bulimia, nausea, vomiting, gaseous distention, diarrhea, en- 



112 PELLAGRA. 

teritis, colitis, and rectitis. Burning in the stomach or pyrosis is 
a variable symptom, present chiefly during the period of outbreak. 
Nausea is common and actual vomiting absent in the milder cases ; 
during severe attacks vomiting is a common symptom. The pel- 
lagrin sums up his gastrointestinal symptoms as sore mouth, in- 
digestion, and diarrhea. Of these indigestion, lack of appetite, 
coated tongue appear first, next the diarrhea, and lastly the sore 
mouth. Even with those patients who say that the dermatosis 
is first, careful and patient questioning will reveal a week or a 
few days of heaviness in the stomach, gas, belching, occasional 
nausea, and that disease known far and wide as "biliousness" may 
have preceded the dermatitis. J. Clarence Johnson, in his 1911 
paper before the American Gastroenterological Association, pre- 
sents the analysis of 20 cases and relates the analyses of the stomach 
contents, the position of the stomach, the diarrhea, to each other 
and more general symptoms. This table (page 113) adds much 
new information to the condition of the stomach and intestines in 
pellagra, and on the relation between the secretion of hydrochloric 
acid and the diarrhea. 

Summarizing the important details of this valuable table, the 
stomach was normal in position in 11 cases, ptosis present in 4, 
and atony in 5 ; nausea was present in 15, vomiting in 7, indi- 
cating a common experience that vomiting is rather the exception 
and present only during the severe cases, or during the acme of 
the outbreak. I have never seen it except in bed-ridden pella- 
grins, and in fatal cases the vomiting is often an accompaniment 
of the diarrhea. Only 3 of the 20 cases failed to have pain in 
the stomach, the gastralgia so accented by Procopiu and Triller. 
The three sensory gastric symptoms in pellagra are pyrosis or 
burning, gastralgia or a real gastric hurt, and bulimia or the 
hungerache. The pyrosis is rather the most chronic symptom of 
the three, often preceding the other gastric symptoms and per- 
sisting during the winter when the others have disappeared. 
These burning pains are probably referred pains, having a common 
cause of origin with the well-known fiery sensations in the hands 
and feet. I can not believe that they arise in the stomach from 
any gastric condition, but are rather due to cord involvement and 
impulses reflected through the sympathetic ganglia. 

The gastralgia may arise without known cause, persist for a 
few days, and disappear. It is rather more chronic than the 



ALIMENTARY TRACT IN PELLAGRA. 



113 



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114 



PELLAGRA. 



bulimia, and is not influenced by food. Indeed, the distinguishing 
characteristic of these sensory symptoms is that they seem to bear 
no relation to food in any way. Pellagrins with severe gastric 
symptoms often suffer as much with an empty stomach as with 
regular diet. As one of them wisely said, "I have pain in my 
stomach and indigestion, whether I eat anything or not." 

With these sensory symptoms, varying in kind and in degree, 
nausea, and often increased saliva, it is no wonder that choking 
sensations and difficulty in swallowing are present at times. The 
pellagrin remarks that he can drink just so much water — to drink 



♦. 








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Fig. 16. — Intestines showing atrophy of the muscles; increase in the connective tissue; 
chronic enteritis; hematoxylin-eosin. (By Dr. Bravetta.) 

any more will choke him, or only so much will run down. The 
nervous exhaustion marked in the outbreak, added to these sen- 
sations of choking and burning, with gaseous distention, often 
causes the complaint that the stomach is full and weighty even 
when no food or drink has been taken for hours. Cough was 
present in 11 cases, and one of these was tubercular. With 
stomatitis and pharyngitis, nausea, and other gastric symptoms, 
the wonder is that cough is not more common and more violent. 
Unless a local pulmonary condition is present, it does not persist 
after the attack is over. 



ALIMENTARY TRACT IN PELLAGRA. 115 

One of the most striking facts in this series of cases is the fact 
that there seems to be a relation between the lack of hydrochloric 
acid and the presence of diarrhea. Only 6 had free acid, and, with 
one exception, diarrhea was absent; in the 14 with absence of hy- 
drochloric acid there was diarrhea. The diarrhea in the one ex- 
ception noted was temporary and due to a different cause. Rennin 
was present in 7 cases, and in those cases with rennin present and 
the acid absent, Johnson noticed that the "diarrhea was less fre- 
quent, less severe, and less persistent." Another striking fact is 
that in no case with free acid has insanity developed or death fol- 
lowed in his experience. Two cases had no gastric juice whatever ; 
in one was pain, frothy saliva, vomiting, diarrhea, and prostra- 
tion; in the other a persistent diarrhea, with dizziness and ocular 
symptoms "without astigmatism." Johnson's argument as to the 
relation of acid absence and diarrhea is confirmed by the ordinary 
observation that in pellagrins, when the stomatitis and esophagitis 
permit, the administration of hydrochloric acid with pepsin has 
more effect on the diarrhea than the ordinary astringents and 
diarrhea remedies. 

Back of the absence of the acid stands another problem — What 
causes the lack of acid? What causes the involvement of the 
alimentary tract as a whole? Is it related to the nervous system 
as an effect, or is it as truly an outcrop of the pellagrous process 
as the dermatosis or the pellagrous neurosis and organic cord 
changes. If the diarrhea is the result of gastric failure, is the 
gastric failure due to a deeper failure of the nerve centers? How 
much are the sympathetic ganglia in the abdomen involved in all 
this? Are they primarily affected as Lombroso thought, or is it 
not rather more in harmony with the facts to consider the sym- 
pathetic ganglia as the playground and meeting place of two dif- 
ferent sets of impulses — one arising in the cord as the result of 
the pellagrous process, and the other in the alimentary tract as 
the result of the pellagrous process there? One is reminded of 
the striking statement of Grurd that pellagra is essentially a dis- 
ease of the epithelial tissues, including the skin epithelium, the 
alimentary endothelium, and the ectodermically derived nervous 
system. 

Out of all these questions and facts emerges one clear conclu- 
sion — changes in the nervous system in pellagra can not be con- 
sidered solely responsible for all the symptoms that in an ordinary 



116 PELLAGRA. 

case of neurasthenia are attributed to nerve exhaustion. The 
stomatitis, indigestion, gastritis, diarrhea, gastralgia, ravenous ap- 
petite, or refusal of food, thirst, or antipathy to water will of 
themselves cause dizziness, vertigo, weakness, neurasthenic con- 
ditions, functional ocular symptoms, and the exhaustion common 
to constant nausea and occasional vomiting. One recalls how great 
an influence a single aphthous ulcer has on his feelings, indigestion 
following a banquet provokes irritability and the blues, diarrhea 
for a day calls for rest, and the combination and increased severity 
of all these in pellagra produces a reflex effect on the nervous 
system and systemic condition that contributes to the f acies dolorosa 
of the pellagrin. 

The diarrhea usually precedes the dermatitis, but it may occur 
simultaneously, and Fritz has noticed that it is common for the 
two to appear together in those whose work keeps them in the sun. 
It also shows that the diarrhea is the symptom of a systemic morbid 
process. The diarrhea, stomatitis, and dermatitis reach their cul- 
mination together during the outbreak. The diarrhea comes grad- 
ually, lasts about a month all told, disappearing gradually as it 
came. In Tucker's 55 collected cases diarrhea was present in 54, 
with remissions in the diarrhea in 36 cases, and diarrhea alter- 
nating with constipation in 30 cases. All my cases except one 
had diarrhea, and, without exception, the more severe the diar- 
rhea the greater the prostration and exhaustion, and the more 
apparently severe the pellagra. In some pellagrins the flux is so 
severe as to merit the title of diarrheic pellagra. The Egyptian 
cases of Sandwith seem to have less diarrhea than either the Italian 
or American. Out of 166 cases the bowels in 103 were normal, 9 
had slight constipation, 46 with slight diarrhea, and 8 with exces- 
sive diarrhea. 

In the height of the spring attack the number of stools in the 
twenty-four hours varies from six to thirty, ten to twenty being 
an average. In my own experience the number of stools is in- 
fluenced neither by rest nor food, and the number is as great in 
the night as in the day, and often worse from 3 to 9 o'clock in the 
morning. In the early part of the attack and in the initial stage 
of the disease the diarrhea is more spasmodic in character and with 
far more peristaltic activity, so that the patient complains of ab- 
dominal pain and griping like a colic from indigestion. The stools 
at this time are thicker, contain more mucous and endothelial cells, 



ALIMENTARY TRACT IN PELLAGRA. 117 

the pellagrous odor is not so pervasive, and the stools do not come 
so freely as in the latter stages. At this time they may be tinged 
with blood, though not so commonly as in acute dysentery. They 
vary from gray and light-brown to green in color. 

In the later stages of the disease the diarrhea assumes a more 
serous character, is more persistent, and far less amenable to treat- 
ment. It is almost a pure watery stool, usually of a light-green 
color, occasionally almost clear. At this time the acute phase of 
the disease may develop, and the diarrhea precede the delirium, 
and foreshadows marasmus and the approach of death. As the 
serous discharges increase, distention develops and paresis of the 
intestinal walls occurs. Rectitis, hemorrhoids, and anal fissures 
add to the cachexia and distress. As a rule, the mild cases do not 
develop a severe diarrhea, and the diarrhea ceases as the attack 
recedes. The diarrhea may be the only symptom of the fall ex- 
acerbation and may last for only a few days; in other cases, after 
the first spring attack, the bowels are always relaxed, and two to 
four stools a day common. In the cases with constipation the at- 
tack is mild and short, and the disease progresses slowly. The 
life of the pellagrin is prolonged in inverse proportion to the 
severity and the persistence of the diarrhea. 

As the disease advances, the entire alimentary tract becomes in- 
flamed; gastritis, enteritis, colitis, and rectitis are the foundations 
for gastric and intestinal ulceration, with blood, mucus, pus, and 
increased putrefaction and fermentation. At this stage indicanuria 
is common. Absorption is interfered with, and there is an increase 
in undigested food materials, especially fats, starch granules, plant 
cells, and muscle fibers. The stools are acid as a rule and gaseous, 
looking as if they had been whipped, so numerous are the air 
bubbles. Under the microscope there is an increase in the fat 
globules, due probably to a decrease in the bile and pancreatic 
juice. If the stool in pellagrous diarrhea is put in a bottle or 
graduate and allowed to stand for several hours, it separates into 
three layers — (1) above is the aqueous portion, serous in char- 
acter, often colored a light-yellow; (2) below this a thick gray 
layer composed of mucus, pus, and occasionally blood cells; (3) 
a heavy layer below, dark-brown or green in color, and composed 
chiefly of waste matter from the food, or ordinary fecal matter, 
in which is found clinging mucus that has not separated. J. D. 
Long in his admirable studies found ammonium and magnesium 



118 



PELLAGRA. 



phosphate crystals, fatty acid crystals, calcium oxalate, cholesterin 
plates, and fungi. 

PATHOLOGY. 

The mucosa of the oral cavity presents hyperemia, occasional 
swelling, ulcerated areas, and infrequently the remains of small 
vesicles. A favorite spot for the vesicles is on the cheek just an- 
terior to the pillars. At times the pharynx, palate, and esophagus 
may be in this same hyperemic condition, with a diffuse ulceration. 




Fig. 17. — Section of liver; hyperemic ; hematoxylin orange. (By Dr. Bravetta.) 

At the summit of the anterior pillars two cyanosed areas, round 
or oval in shape, are often found. The tongue presents fissures, 
absence of its epithelial coat, and engorgement of the veins on 
the margins and beneath. Ulcers may be present on the tip and 
anterior lateral margins. 

The stomach is found normal in position and size, or gastro- 
ptosis occurs, and I believe more frequently than the records would 
show, and dilatation is present infrequently. "Watson reports a 
case in which there was excessive redness of the peritoneal coat 
noted during a laparotomy. Post-mortem, the organ is rather pale, 



ALIMENTARY TRACT IN PELLAGRA. 



119 



the muscles atrophied, the walls thinned, and the internal walls 
covered with mucus. In the more acute forms the classic picture 
of a gastritis is present, with redness of the mucosa and marked 
ulceration, especially in the pyloric region. 

The intestinal changes are variable, depending on the length and 
the severity of the disease. The intestine is usually emaciated and 
thinned in proportion to the rest of the body, though it is not true 
that the walls are always atrophied, especially throughout their 
entire course. As a rule, the intestine is atrophied, brown pig- 
mentation is often present, and the muscular coat thinner than 




Fig. 18. — Spleen, showing increase in connective tissue: 

Bravetta.) 



hematoxylin orange. (By Dr. 



normal. Labus thought the intestinal canal was contracted through- 
out, a point not confirmed altogether by later investigators. With 
acute cases and enteritis, ulceration may occur at any part of the 
large or small gut. With ulceration, hyperemia instead of anemia 
is present in more or less localized sections. Ulcers may form in 
the duodenum, jejunum, and ileum — more frequently in the last 
two divisions ; ulceration may occur in the large intestine, but most 
often in the rectum. The mouth and rectum are the most fre- 
quent areas in the alimentary tract for pellagrous inflammation. 
The anus is often swollen, discolored, and fissures and hemorrhoids 



120 PELLAGRA. 

are occasionally found. The diarrhea is the cause of these fissures 
and hemorrhoids, and the resulting irritation. 

The liver varies from atrophy to hypertrophy ; in far the greater 
number of cases it is atrophied. This is a simple atrophy due to 
malnutrition, cachexia, and marasmus. The decrease in size may 
be very marked, even to one-third the original size. The edges are 
sharp, the capsule wrinkled, and the gall bladder may project be- 
yond the lower border, often dilated and engorged with bile. 
Fatty degeneration, cloudy swelling, or brown atrophy may exist 
in the liver cells. The liver is frequently tough, and pale like 
the liver in senile anemia. The pancreas is usually small, tough, 
and friable. The spleen may be normal, but it is usually atrophied 
and tough. In his report on case 6 of his post-mortems, Strambio 
notes the spleen weighed twenty-seven pounds, with no other com- 
ment. This was probably a malarial spleen, as in all his other 
cases the organ was normal according to his report. The mesenteric 
glands are often enlarged. 



CHAPTER V, 

THE SKIN IN PELLAGRA. 

Hebra, in the first volume of his famous work on " Diseases of 
the Skin," classifies pellagra as a skin disease in the group which 
he describes as "acute, exudative, but noncontagious dermatosis." 
He makes a second division which he calls "the polymorphous 
erythemata, ' ' and includes pellagra there, believing it to be not an 
inflammation of the skin alone, but depending rather on a toxic 
action affecting the whole organism. 

"The symptoms of the erythematous inflammation of the skin 
consists in rose or blood-red discoloration, disappearing under pres- 
sure, and in a slight degree of swelling, caused by serous exudation 
or edema. In this affection the tension of the skin is inconsid- 
erable, and little or no pain or itching is complained of. Its course 
is always acute, and its chief peculiarity is that it generally ter- 
minates in the absorption of the inflammatory products, followed 
by deposit of pigment or desquamation of the cuticle. It rarely 
happens that either vesicles, bullae, or pustules develop themselves 
in this form of dermatitis; and there is never any deeply seated 
suppuration, attended with loss of substance, or followed by the 
formation of cicatrices. The erythematous inflammation involves 
only the superficial layers of the cutis, while the phlegmonous in- 
volves the whole skin and the connective tissues beneath." 
(Hebra.) 

Howard Fox very wisely believes the red erythema in pellagra 
to be a true dermatitis, and not a simple erythema. Hebra was 
of the same mind, and the sooner we come to their belief the better. 
Fox adds this important statement: "It would seem quite proper 
to use the term erythema for the first stage of the disease, which 
resembles an ordinary sunburn and which lasts only a few days. 
But it seems somewhat anomalous to speak of the entire eruption 
as an erythema when the erythematous stage is so comparatively 
insignificant, while the stage of desquamation is so characteristic 
and of such long duration." In reading a case reported by Turck 

121 



122 



PELLAGRA. 



occurs this sentence, and, taken with the statement of Fox, the 
problem of the skin in pellagra will become easy: " "Within two 
weeks after the operation these patches increased in extent, and 
there was a condition resembling in places a dry eczema and in 
others an erythema.' 7 Here is the clue to the whole matter. The 
pellagrous skin is dimorphous. It is a dermatitis, which is called 
also the eruption, the erythema, or the pellagrous exanthem. It 
is also a dermotagra, or a rough skin, which is called the dry 




Pig. 19. — Dermatitis on hands. A clear band of skin is shown on left hand where ring 
was continually worn, and a darker band is shown on ring finger of right hand where 
ring was occasionally worn, indicating the influence of light. (Courtesy of Dr. C. C. 

5.) 



eczema or branny skin of pellagra, or the eczematoid condition 
of the skin in pellagra. With this idea of a double affection of 
the skin in pellagra, I think we can trace the origin of some of 
the early synonyms of the disease. In Spain it was called "mal 
de la rosa," named from the rose-red inflammation of the hand. 
In Italy among the common people originated the pellis agra, or 
rough skin, because the Italians named it from the roughness so 
markedly apparent above and around the dermatitis and on the 
elbow and body, and persisting in some cases on the original der- 



THE SKIN IN PELLAGRA. 



123 



matitis area. It is a mal de la rosa because it is a rose-red derma- 
titis; it is a pellis agra because it is a dermotagra or rough skin. 
The following diagrammatic arrangement permits us to discuss 
separately the two divisions: 



Dermatosis of pellagra- 
dimorphous. 



1. Dermatitis, or in- 
flamed skin. 



2. Dermotagra, or rough 
skin. 



"a. Erythema, maculo- 

papular. 
<; b. Erythema, vesicles 
and bullse. 
c. Fissures. 

a. Eczematoid. 

b. Keratoid. 

c. Follicular. 



In the majority of cases the dermatosis is a dermatitis of the 
maculo-papular type with the dermotagra of the eczematoid type. 
The dermatitis with vesicles and bullae is far less frequent, involves 
the skin to a greater degree than the first type of dermatitis, and 
generally indicates a severe pellagrous attack internally. Fissures 
develop rarely, and the area of inflammation about them is de- 
pendent on their length and depth. Taking a pellagrous dermatitis 
limited to the back of the hands and wrists, and a dermotagra 
around the borders of the dermatitis and extending up the extensor 
surface of the forearm to and including the elbow as a type, the 
order of the development is as follows, as illustrated by a diagram 
from Merk, slightly altered: 




= B 

Fig. 20. — Diagram illustrating the development and course of the pellagrous dermatitis. 

The beginning of the dermatitis is represented by a, when the 
influx of blood and serum into the dermis is marked; 1 to 2 marks 
the erythema at the time when the livid red hue is most prominent ; 
b represents the increase in the dermatitis, c its maximum develop- 
ment, d and e mark the gradual recession of the dermatitis and 
the erythema. At / the stage of dermatitis may be considered over, 
and the shedding of the epithelium begins. As the dermatitis re- 
cedes, the shed epithelium becomes evident, but, what is important, 
this continues in fine, branny scales, and marks a permanent change 



124 



PELLAGRA. 



in the dermatitis area; it becomes hyperplastic, and in a great 
many cases remains eczematoid, feeling rough and shedding fine 
scales. This is indicated by g; the line f g does not again coincide 
with the basal line of skin smoothness, A B, except in mild and 
rare cases. 

Above the wrist and occurring with the dermatitis is the typical 




Fig. 21. — Insane pellagrin, with a typical dermotagra in palm of hand. 

Bravetta.) 



(Courtesy of Dr. 



dermotagra. It involves the flexor surface of the forearm and the 
elbow-joint over the olecranon process. Usually it is eczematoid 
in character, partaking in appearance and feeling of a dry, scaly 
eczema; but there is often a noticeable prominence of the hair 
follicles, and the elbow may be so rough, wrinkled, and laid off 
in small rhomboid and rectangular areas that it assumes a keratoid 
condition. This last is especially true in old cases, and is most 






THE SKIN IN PELLAGRA. 



125 



often seen in asylums for the insane. I have seen it both in Amer- 
ica and in Italy. 

As Watson very wisely remarks, the dermatitis with vesicles and 
bullae "differs only in degree" from the maculo-papular type as 
above. When the vesicles occur, the dermatitis is known as the 
"wet" form as distinguished from the "dry." Even this wet 
form differs very much in severity. The dermatitis may be of the 
ordinary erythematous type, and a few small vesicles may develop 
in the center of the back of each hand. These are usually small 
and discrete, contain serum, occasionally blood-streaked. The epi- 




Fig. 22. — Pellagrous dermatitis ; dry form, with exfoliation of the skin. 

Dr. Bravetta.) 



(Courtesy of 



dermis is elevated, serum quickly exudes, and a common blister 
results. It ruptures, the base is raw, heals quickly, and rarely in 
the mild forms leaves a scar. In the more severe cases the vesicles 
become bullae, cover the back of the hand ; edema occurs, and small 
vesicles may occur on the fingers. On Siler's cases 10 percent 
had the vesicles, and 66 percent of the cases with vesicles died. 
The presence of blisters indicates usually a severe attack of the 
disease. Occasionally they become purulent, with a phlegmonous 



126 PELLAGRA. 

involvement of the deeper structures. After rupture, ordinary 
granular tissue with the small elevations are seen as healing takes 
place. Either here or in the more severe dry form, fissures may 
develop, with gaping and localized inflammation. Favorite seats 
are between the metacarpal bones, over the knuckles, and between 
the fingers. 

The pellagrous dermatosis is a part of the pellagrous process — 
it is pellagra of the skin. One asks why the skin is affected in 
pellagra. There is no more an answer to this question than to 
the other view — why should the skin not be affected in pellagra? 
Measles begin on the face and scarlet fever on the body; the 
reason is not clear, and one can only say that it is a characteristic 
of the disease in question. The rose-red spots of typhoid select 
the abdomen and the dermatitis of pellagra selects the hands, and 
the selective action of different diseases on different organs and 
in different locations is as inexplicable as is the specific action of 
different pathogenic bacteria. 

Even with the knowledge that the dermatosis is the skin ex- 
hibition of the disease, it is well to remember that the internal 
malady may continue to exist independently of the eruption or of 
its disappearance. When the dermatosis goes, it does not mean 
that the pellagra has gone. The eruption does not kill, but pel- 
lagra does kill. The dermatosis is the least of the dangers to the 
pellagrin, but the most important of the symptoms to the phy- 
sician in diagnosis. It is the passkey and the capstone to the 
correct diagnosis of the disease. In the language of Roussel, it 
is the "element decisif dans le diagnostic." The existence of pel- 
lagra sine exanthemata is relatively infrequent, and in all ordinary 
cases of pellagra the decisive element is the dermatosis. It may 
be so slight as to hardly differ from a slight sunburn and last 
only a few days in its entirety, though the dermotagra on the 
forearms and elbows usually lasts longer, but this skin involve- 
ment is the decisive and conclusive element in the diagnosis. In 
the language of Hyde, it is "the local expression of a systemic 
disorder. ' ' 

Eruptions in systemic diseases are common, and, viewed in this 
broad light, there is nothing remarkable in the presence of the pella- 
grous dermatosis. Syphilis has an eruption, and in suspected cases 
the physician may postpone treatment and wait for the appearance 
of the rash, because it is confirmatory and diagnostic rather than 



THE SKIN IN PELLAGRA. 



127 



dangerous. Scarlet fever, measles, smallpox, and rotheln each 
furnish their peculiar rash and eruption, with its individual char- 
acteristics, time of appearance, and duration, and pellagra does 




Fig. 23. — Dermatitis. It is symmetrical, and is called the pellagrous glove, 
lagra Report of the Tennessee State Board of Health.) 



(From Pel- 



likewise. As Merk well says, "the cutaneous symptoms in pellagra 
are of the same importance from the point of view of diagnosis 
as in chickenpox, smallpox, scarlet fever, and measles. ' ' 



128 PELLAGRA. 

The color of the dermatitis varies according to the stage of the 
attack and the length of the disease. At the beginning it is the 
color of red cedar, with a tint of pink added; at the acme of 
the attack it is the color of red cedar, with a greater and more 
marked redness ; at the decline of the dermatitis it is like red cedar, 
with a darker tint added. If one takes a smooth piece of the heart 
of red cedar wood, and compares it with the pellagrous dermatitis, 
he is at once struck with the similarity and with the fact that the 
brownish-red color of the cedar is the fundamental color of the 
various stages of the dermatitis. In the lighter attacks the simi- 
larity with sunburn is to be borne in mind, and at times in these 
mild forms the dermatitis is indistinguishable in tint from ordinary 
pigmentation caused by the sun. In the more severe forms it turns 
to sepia toward the close, and especially if there have been several 
previous attacks. On the face there may be a dermatitis with a 
marked redness, and at times one thinks of a brick-red color or 
even the lighter hue of terra-cotta. 

In the dermatitis with vesicles and bullae the redness is more 
apparent, and in the general development the similarity to a burn 
first pointed out by Babcock may become evident. These vesicles 
break and heal, and leave a hard, scabby covering darker than the 
surrounding skin. During the dermatitis the skin is smooth, 
glistening and shiny, and may appear tense and very slightly 
swollen. In the negro the dermatitis is either stark black, like 
soot or a black hat, or at certain angles a gray tint may be apparent. 
Marie noticed this gray hue in the Arabs in Egypt. At times this 
skin in the negro may peel off in large, thick plates, perfectly black 
in color, and as thick as skin from the sole of the foot of the negro 
in typhoid. Here the lamellae are hard and dry, and more like 
plates than pieces of skin. Ecchymosis may appear on the body 
during the dermatitis or in the dermatitis area after the exfolia- 
tion has begun. 

The dermotagra occurs simultaneously with the dermatitis, but 
usually on the flexor surface of the forearms, elbows, occasionally 
on the arms, face, and other parts of the body. The branny rough- 
ness may be in color and appearance similar to a dry, scaly eczema, 
except there is usually a brownish tint present and the flexor 
surface of the forearm and the elbow look dirty as if in need of 
soap and water. The smooth and glistening appearance of the 
dermatitis area is absent, and dirty roughness persists. On the 



THE SKIN IX PELLAGRA. 129 

elbow, face, knees, and at times on the trunk even, the slight brown- 
ish tint is absent and only the roughness is noticed, with the 
shedding of small branny scales when rubbed or scratched. I have 
seen cases in which the maculo-papular dermatitis, after exfolia- 
tion and all signs of the inflammation and pigmentation had gone, 
was succeeded by a persistent dermotagra on the back of both 
hands and the flexor surface of the forearms. The patient may 
seem and feel well, and yet on close observation this suspicious 
dermotagra can often be seen. This is one of the strongest evi- 
dences presented by the skin in the periods of intermission and 
when no other symptom remains of the previous dermatosis. 

Another aid afforded by the skin in the periods of intermission 
is what Sandwith calls "the preternatural pinkish cleanliness" of 
the finger tips, and he might have added of the toes also. At times 
this pink cleanliness includes the palmar surface of all the fingers, 
and it is especially evident when the arms hang down or when the 
hand of the pellagrin is put by the side of the hand of a healthy 
person for comparison. The tips of the fingers seem as clean be- 
tween the attacks as the back of the hands seem dirty during the 
attack. This condition is especially evident in the better class of 
pellagrins. Along with the abnormal pinkness on the palmar sur- 
face is found the increase in the number of folds or wrinkles over 
the first interphalangeal joint, and the division of these folds into 
small areas, which are square, rhomboid, or rectangular in shape, 
and rather rough. After the attack these folds hang loosely, are 
increased in number over the usual three to five wrinkles, and, 
when gently rubbed by the index finger, feel rough. A laborer's 
hand may have these rough divisions, but the pinkness of the fingers 
and reduplication of the folds is absent. 

Another factor in diagnosis between attacks in regard to color 
is the mosaic mottling of the back of the hands, and a cyanotic 
condition of the whole hand when the arm hangs loosely by the 
side. The same condition prevails after the dermatitis on the foot. 
One can sometimes examine the hand of a pellagrin during the 
winter months after the attack of the previous spring, and the pink 
fingers, mosaic mottling and cyanosis, increased wrinkles and rough 
areas are of great aid in doubtful cases. I have been able to bring 
all these symptoms out more clearly by lightly grasping the wrist 
with my hand and interfering with the circulation. In one case 
the perspiration burst forth quickly all over the palm of the hand, 



130 PELLAGRA. 

and the cleanliness of the pink fingers was wonderful. The hands 
of the pellagrin can not be too closely studied. 

LOCATION. 

The location of the dermatosis is influenced by the selective action 
of the disease, by symmetry, and by light or heat. Merk, with the 
aid of Weiss, collected pellagra statistics in the south of the Tyrol 
for the years 1905-1907. These observations included 384,072 in- 
habitants, of whom 4,836 were pellagrins, or 13.4 per thousand; 
of these, 2,973, or 61.4 percent, presented some of the cutaneous 
manifestations of pellagra; and 2,179, or 45 percent of the cases, 
presented the maculo-papular dermatitis. Of these last the follow- 
ing notations were made : 

1,677, or 77 percent, with dermatitis on the back of both hands. 
283, or 13 percent, with dermatitis on the back of both hands and on 

the neck. 
164, or 7.5 percent, with dermatitis in rare locations and on the neck. 
53, or 2.4 percent, with dermatitis on other parts of the body. 

This table gives ample proof of the selective action of pellagra on 
the skin. The back of the hands is the most favorite spot, then 
the neck; in America the feet, face, and then other parts of the 
body. To the selective action is added the symmetrical distribu- 
tion, the dermatitis or the dermotagra usually appearing on 
bilateral areas simultaneously. There are exceptions even to this 
simultaneous action. Echols at Milledgeville showed me a female 
pellagrin in his wards on whose right hand the characteristic 
dermatitis appeared, and after eight days it appeared on the same 
area on the left hand. Tucker reports the only other case of this 
kind I have found in the literature. He gives in his 55 collected 
cases 44 in which the dermatosis began on the back of the hands 
and forearms; in 7 on the back of the hands, forehead, and alae 
of the nose; in 3 on the back of the hands and feet, and in 1 on 
the back of the hands and neck. The dermatosis remained con- 
fined to the hands and forearms in 28 ; hands, face, and neck in 4 ; 
hands, face, feet, and neck in 12. In one case the skin was in- 
volved all over the body, the pellagra universalis. In this form 
the dermatitis is limited usually to the ordinary sites of hands, 
face, neck, and feet, and the rest of the body covered with the 



THE SKIN IN PELLAGRA. 



131 



eczematoid dermotagra. I saw a case of this kind in Italy at 
Mombello, and one case in Georgia even more remarkable, as there 
was a dermatitis on the hands and wrists, between the scapulae, and 
in the sacral region, extending down in the gluteal folds. 

On the hands the dermatitis usually covers the backs, affecting 
least the terminal phalanges, and it usually extends from two to 
four inches above the wrist as the pellagrous glove. The eczema- 
toid dermotagra then usually extends above to and including the 
elbow. At times the dermatitis extends as far as the elbow, or 
it may skip the elbow and reappear on the arm or under the 




Fig. 24. — An Italian case of senile hands in pellagra. The skin is dry and wrinkled, and 
lies over the knuckles in folds. (Courtesy of Dr. Bravetta.) 

axilla. In advanced or severe cases the dermatitis surrounds the 
wrist, appearing in triangular form anteriorly as the pellagrous 
bracelet. The feet, when affected, are covered on the dorsum from 
the toes to the malleoli, but the dermatitis may extend up the leg 
for a variable distance, as a rule not above the junction of the 
lower and middle thirds, forming the pellagrous boot. The knees 
may be covered, like the elbows, with the keratoid roughness, dirty- 
brown in color, and the legs may present a mottling anteriorly to 
the knees. 

After the dermatitis departs and the epidermis exfoliates, the 



132 PELLAGRA. 

dermotagra persists for a variable period, often permanently. 
Contrary to Jansen and the Italian writers, it may invade the hand 
as the keratoid dermotagra. Bravetta had a case at Mombello 
in Italy. Here the dermotagra invaded the palm from the radial 
side, advancing under the thumb. This invasion of the palmar 
surface seems more common in America than in Italy. I have 
seen several cases where it advanced from the ulnar side, and Zellar 
in Illinios has seen cases on the soles of the feet, with peeling as 
in scarlet fever. In negroes the elbows and knees are often covered 
with persistent ashen-gray roughness, noticeable between attacks. 

A discrete dermatitis may occur around the lips, or the pella- 
grous mask may cover the face with exfoliation. The forehead 
may be affected with the eczematoid roughness, or mingled with 
these may be the isolated areas of dermatitis. The dermatitis may 
stimulate the sebaceous glands and produce a temporary seborrhea. 
This is more common on and around the nose than elsewhere. A 
symmetrical dermatitis may appear over the malar bones, below 
and behind the ears, and crescentic ecchymosis, dermatitis, or 
dermotagrous spots, always symmetrical, develop on the lower and 
upper lids. The symmetrical areas of dermatitis may appear on 
the back of the neck, or a crescentic area cover the back of the 
neck, concavity upward, and thickest in the median line and ex- 
tending the same distance on both sides. The dermatitis may sur- 
round the neck with a sternal prolongation, which forms the Span- 
ish cravat of Casal. Sand with has seen this in Egypt, and thinks 
it due to the open shirt-front of the field laborers. Studying 
many hundred cases of pellagra, one sees either the dermatitis or 
the dermotagra in locations rarely described, and which Bravetta 
well calls "atypical locations." These are in the axilla, on the 
flexor surface of the elbow- joint, the posterior surface of the knee, 
on the thighs, the scrotum, a dermotagra making a girdle around 
the hips, and Dr. Greene at Milledgeville showed me a remarkable 
case in a young negro with a severe dermatitis entirely around the 
shoulder, covering an area about four inches wide and making a 
veritable shoulder girdle of dermatitis, coal black in color. After 
the attack is over, walnut stain effects are occasionally seen on the 
face on the order of chloasmic spots. This colored area may persist 
as a permanent pigmentation without any roughness. 

The perineum, vulva, and anal regions in the female are attacked 
by the dermatitis, occasionally by gangrene, and even a pro- 






THE SKIN IN PELLAGRA. 133 

nounced keratoid condition may be present. In the more serious 
cases the dermatitis may extend from the inner surface of the 
thighs upward and backward to the anus and the gluteal region. 
An acute vaginitis may be present, with a mucopurulent discharge, 
erosion of the epidermis, and even sloughing of the tissues. The 
dermatitis may occur on the folds of the labia majora and minora, 
but the inflammation of the vaginal mucosa is similar in character 
to the stomatitis. The dermatitis with vesicles is not infrequent 
when the hands have the same inflammation, and in these cases 
sloughing and gangrene may develop in the vulvar region a short 
time before death. J. Clarence Johnson, of Atlanta, had a case in 
which the vulva and labia majora were covered with a thick, kera- 
toid covering, very rough and dry to tne touch. The patient re- 
covered from the attack, and after exfoliation the vulva was 
normal. 

RELATION OF THE DERMATOSIS TO LIGHT. 

In the early days of pellagra the sun was believed to cause the 
disease, and it was called mal de la sol, or sickness of the sun. 
Jansen remarked that the sun was neither hotter nor different in 
Italy than in other sections of the world where the disease did not 
exist, and the dermatitis may occur on parts of the body covered 
by clothing. In those exposed to direct sunlight the dermatosis 
in pellagra seems to appear earlier in relation to the other symp- 
toms, and to be synchronous with the diarrhea, whereas in those 
living indoors the diarrhea or dyspepsia usually precedes the der- 
matitis. This influence of the sun has been attributed to the 
shorter or violet rays of the spectrum, known usually as the actinic 
rays. The work of Aaron would seem to weaken the actinic theory 
in pellagra, and to cause the belief that the direct heat of the sun 
was the real influence, with the elevation in temperature of the 
parts exposed to the sun and of the surface temperature in general 
as the chief heat factor. Various experiments have been performed 
with fenestrated gloves. The pellagrous glove itself often extends 
from four to six inches above the lower border of the sleeves. Bass ' 
ring experiment (Fig. 19) seemed to show protection from the der- 
matitis when the parts were not exposed to the sun. This much is 
certain, and proof that the influence of the solar heat is only a very 
minor influence — a patient must first have pellagra internally be- 



134 



PELLAGRA. 



fore the sun can cause or influence the dermatitis externally. The 
disease, and not the sun, causes the pellagrous dermatitis. 

The hair is usually not affected in those developing pellagra 
during adult life, but in children the hair is often short, thick, and 
coarse, lacks the usual amount of sebaceous matter, and feels rough. 
It stands up, and does not respond to combing and brushing as 




Fig. 25. — Wet form of dermatitis, with sloughing of skin. Unusual lesions in the palms 
of the hands, due to wringing clothes when washing. The elbows are also affected 
from pressure when rising from the bed. (Courtesy of Dr. C. C. Bass.) 

ordinary hair. In children the hair on the body does not develop 
normally, but is both scant and short. 

The perspiration, normally acid, may in pellagra be neutral. 
Procopiu found it neutral in 20 cases, acid in 2, and alkaline in 3. 
In Tucker's 49 cases it was normal in 14, increased in 3, and de- 
creased in 32. In insane pellagrins it has seemed to me that it 



THE SKIN IN PELLAGRA, 



135 



was noticeably increased on the feet and hands, and the more ad- 
vanced the nerve lesions the more variable the amount of sweat. 
The odor of the body is increased in certain cases, and this is at- 
tributed to the fetid sweat. The sebaceous glands of the skin are 
at times overactive — more pronounced, as is to be expected in 
young pellagrins. 

The nails are occasionally affected. They turn white or grayish 




Fig. 26. — Rough hands of a pellagrin as contrasted with the normal hand of a hospital 

orderly. (Courtesy of Dr. Bravetta.) 

white, are thick, and in the spatulate hand are very wide and brittle. 
This is a rare occurrence, and occurs usually in advanced cases — 
especially in the insane and following a hemiplegia in old pella- 
grins. Here it is probably trophic in nature and dependent on 
the pellagrous process in the nervous system. It is found in the 
asylums for the insane rather than in pellagrins in private practice. 
Occasionally the nails fail to receive sufficient nourishment from 
the blood and actually drop off. Such trophic changes rarely occur 
in private practice. 



136 



PELLAGRA. 



SENSORY SYMPTOMS. 

The sensory symptoms in ordinary cases consist of either tense- 
ness or tightness of the skin over the dermatitis areas and in those 
with vesicles, bullae, and swelling ; itching sensations ; and, lastly, 
the most constant and irritating of the three is the burning of 
the hands and feet, and infrequently other parts. For a few days 
before the eruption the skin may feel tense and tight as if it were 




Fig. 27. 



-An Italian case of typical dermatitis, showing the feet during an attack. 
(Courtesy of Dr. Bravetta.) 



being stretched or the hand and forearm were swelling. This is of 
short duration, reaches its maximum at the height of the derma- 
titis, and recedes rapidly with the exfoliation. In the dermatitis 
with vesicles — the wet form — the swelling and tenseness may be 
increased even to a condition of edema in the inflamed parts, with 
the hands swollen and heavy. After rupture of the bulla?, this 
tightness of the tissues and edema rapidly ceases. 

The itching is a minor symptom, and patients complain of it 



THE SKIN IN PELLAGRA. 



137 



very little. Sandwith, in his 164 cases, had itching in 71, burning 
in 3, and in 90 neither symptom was present. In the American 
cases the percent of burning would certainly rank much higher, 
and the patients complaining of itching much less. Indeed, one 
seldom notes itching sufficient to cause scratching to any degree. 
Whatever actual pruritus exists is apt to be heightened by burning 
sensations, and it is the heat rather than the itching that causes 
the discomfort. The burning may occur on the back between the 
scapula?, over the sacrum or coccyx, and it may be intense around 
the anus and in the perineal region. It may cause insomnia, and 




Fig. 28. — Pellagrous dermatitis. Hand swollen and edematous. (Courtesy of Dr. 

Bravetta.) 



the patient complains that if the burning would only stop he could 
sleep without trouble. Warnock thinks there is a connection in 
the pellagrous insane between the sensations of burning and the 
well-known complaint of discomfort and delusions of being burnt, 
of sorcery, and of persecution. The area of burning may become 
red in the periods of intermission, and in the advanced cases the 
burning often continues long after the attack has receded. This 
burning is probably central in origin along with the burning felt 
in the stomach at the height of the attack. In the advanced 
neurasthenic stage, with mental failure, the burning causes a de- 



138 



PELLAGRA. 



sire for cooling and for water, and many of the suicides by drown- 
ing formerly common in the Tyrol can be explained in this way. 
One of my cases had no itching or burning, but developed the most 







Fig. 29. — A Georgia case, showing exfoliation of the skin following a spring attack. 
Period of recession. (Courtesy of Dr. J. O. Elrod, Forsyth, Ga.) 

persistently cold nose I have ever seen. It was cold to the touch, 
and the patient said the tip seemed changed to a small piece of ice. 

CHANGES IN THE SKIN. 

The subcutaneous fat and areolar tissues disappear in proportion 
to the severity and the length of the disease. In any case with a 
marked dermatitis there is an atrophy of the skin, with wrinkling 
and often even folds, so that one is struck with the youth of the 
pellagrin and the senility of the skin. The hands are those of old 
people, and the face may look old as a result of the wrinkling and 
puckering of the brow. By pulling up the skin on the back of 



■>' 



THE SKIN IN PELLAGRA. 



139 




Fig. 30. — An Italian case of alcoholic erythema, due to alcohol and not to pellagra. 

(Courtesy of Dr. Bravetta.) 




Fig. 31. — An Italian case of alcoholic erythema, due to alcohol and not to pellagra, and 
of the same character as Fig. 26. (Courtesy of Dr. Bravetta.) 



140 



PELLAGRA. 



the hand, it is loose and there seems too much of it — a condition 
that Italians call "pelle elastica." After two or more attacks of 
dermatitis the skin is permanently atrophied, and the site of the 
inflammation is covered with a thinned, cicatriform, parchment- 
like integument — this last being often irregularly altered — and the 
thinning showing occasionally in stripes parallel with the long axis 
of the hand. (Hyde.) The skin becomes permanently pigmented 
and discolored, and there may be a universal bronzing. The 
eczematoid dermotagra may become permanent in the dermatitis 




Fig. 32. — A close view of the rough skin in pellagra, showing areas of exfoliation, 
swollen and edematous. (Courtesy of Dr. Bravetta.) 



Hand 



area as well as in the original site of the roughness on the fore- 
arm, elbow, and face. 

The microscopical changes are like those of a mild acute inflam- 
matory condition, with a degeneration of the upper layers of the 
dermis. The skin in the beginning of the dermatitis is hyperemic, 
with an exudate of serum and leukocytes, and with no change in 
the superficial and terminal nerves. (Harris.) Following the 
degeneration with the involvement of the connective tissue around 
the blood vessels, repair begins with an increased cellularity of 
the dermis, the presence of fibroblasts, pigmentation, eczematoid 



THE SKIN IN PELLAGRA. 



141 



scaling and shedding, and with an increase in the lymphocytes and 
plasma cells. The sweat and sebaceous glands are hypertrophied 
and enlarged. There is an increase in the number of capillaries, 
with a corresponding increase in the thickness of the skin in the 
prickle cells and stratum granulosum. In ulceration the epidermis 
is absent, and there is loss of substance in the upper part of the 




Fig. 33. — Pellagrous dermatitis. 



Hand swollen and edematous. 
Bravetta.) 



(Courtesy of Dr. 



dermis. As atrophy continues, the epithelium dips deeply into 
the thinned connective tissue. Gurd believes the irritant is in the 
dermis, with the addition of some predisposing factor. There is 
an enormous increase in the formation of pigment in the cells, and 
an increase in the number of chromatophores in the upper dermal 
layers. The pigmentation originates in both types of cells, and, 
so far as is known, remains where it originates. 



CHAPTER VI. 

NERVOUS SYSTEM IN PELLAGRA, 

The pellagrin is the warehouse of all the symptoms of neuras: 
thenia. The very name and presence of the disease causes him to 
fear and to forebode. The dermatosis gives him a sense of filth 
and repugnance; the gastrointestinal condition reacts on him both 
mentally and physically ; and added to these are the deeper tissue 
changes in the cerebrospinal axis, which constitute the organic 
basis for what is at first a neurasthenia, and which later is the 
worn-out soil in which spring up tremors, pains, increased reflexes, 
palsies, paretic and spastic gaits, trophic changes, mental retarda- 
tion, and finally psychoses of different types, inanition, and death. 
The pathological changes in the nervous system are definite in 
varying limits, and their study clears the clinical nerve symptoms 
of much uncertainty. Like the course of pellagra, these changes 
in the nervous system are slowly progressive in the chronic forms 
and rapidly progressive in the acute forms. Progression applies 
as well to the tissue changes as to the external clinical symptoms. 

TISSUE CHANGES. 

The Brain. 

Gross Changes. — The pia mater and arachnoid are thickened 
with occasional thickenings of the dura. The piarachnoid may be 
opaque and milky, with purulent deposits under the arachnoid or 
hemorrhagic ecchymosis. Osseous plaques may be formed and a 
typical lepto-meningitis exist. The brain and its convolutions, 
especially the frontal, show atrophy, and the weight of the brain 
is decreased in the majority of cases. The brain may be partially 
or completely edematous or hyperemic, with excess of fluid in the 
ventricles. It may be anemic, and harder on one side than the 
other. The cerebellum is either small and hard, or edematous and 
soft. These gross changes are variable, as shown by the fact that 
the brain may be either increased or decreased in weight. War- 

142 



NERVOUS SYSTEM IN PELLAGRA. 143 

nock found the brain weight 1,300 grams, with body weight of 46 
kilograms, in an old pellagrin 45 years old, who was "passive, 
prostrate, and demented. " 

Microscopical Changes. — The capillaries show pigmentation and 
fatty degeneration in their walls, and occasional calcareous de- 
posits. The small arterioles and capillaries are filled with blood 
and the perivascular lymph spaces dilated. This condition ex- 
plains the increased fluid found in the ventricles in certain cases. 
The cortical nerve cells show degeneration, with swelling, vacuoles 
form, the nuclei and nucleoli are swollen and pushed to one side. 



- 






, 




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t 


4* 














1 








i 








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i 



Fig. 34. — Cortical cells. Pigmentary degeneration. Method of Cajal. (By Dr. Bravetta.) 

The granules disintegrate in advanced cases, and the dendrites 
swell and break. The neuroglia cells, especially around the vessels, 
swell, and Babes and Sion found small collections of lymphoid 
cells, but this latter was not confirmed by Harris. There is atrophy 
of the degenerating cells and also degeneration of the fibrillar 
structure in the cell body. Harris studied the cells of the cerebel- 
lum and noted degeneration, atrophy, and at times disappearance 
of many of the cells of Purkinje. In one instance he found the 
molecular and granular layers separated by microscopic spaces 
that probably existed during life, 



144 



PELLAGRA. 




Fig. 35. — Cortical cell, showing contraction of the protoplasm. Method of Cajal. 

(By Dr. Bravetta.) 




Fig. 36. — Cells from the spinal cord, showing thickening and contraction of the neuro- 
fibrillar net, or special net of Marinesco. Method of Cajal. (By Dr. Bravetta.) 



NERVOUS SYSTEM IN PELLAGRA. 



145 



The Cord. 

Gross Changes. — These gross changes are not as evident in the 
cord as in the brain. In acute pellagra an acute meningo-myelitis 
may be present, with inflammation of the meninges and a superficial 
edema and softening. The superficial vessels are dilated. 

Microscopical Changes. — These changes include chiefly degen- 
eration in the direct pyramidal tract and in the posterior column, 
including both the tracts of Goll and Burdach. The gray matter 




Fig. 37. — Cells from the spinal cord, showing partial thickening and contraction of the 
neuro-fibrils. Method of Cajal. (By Or. Bravetta.) 



and the spinal ganglia are affected to a degree. A tabular sum- 
mary follows : 

1. Tracts. — The tracts of Goll and Burdach show degeneration 
and a profuse proliferation. These tracts are pale compared with 
the rest of the cord. Occasionally degenerate roots entering in 
lumbar region can be traced up into the dorsal region. There may 
be degeneration of the posterior roots and an increase in the con- 
nective tissue around these roots, with occasional thickening of the 
arteries. The degenerate areas in stained preparations show like 
small spots of ink spattered all over the posterior column. 

2. Direct Pyramidal Tract. — There is more or less degeneration 



146 



PELLAGRA. 



and scattered areas from which the nerve fibers have disappeared. 
Occasionally swollen axis cylinders are fonnd. (Spiller.) 

3. Gray Matter.-^-There is pigmentation of the cells of the 
anterior and posterior horns. The recticulum of many of the cells 
is clearly evident, and the fibrils appear contracted and the cell 
smaller. The degeneration in the cells of the posterior horns ap- 
pear degenerated from the cervical region downward, and espe- 
cially are the cells in Clarke's column affected. Spiller found cells 
in the anterior horn in the lumbar region degenerate, the cell body 
swollen, the nucleus displaced to the periphery, dendrites gone, and 




Fig. 38. — Cell from spinal ganglion. Pigmentary degeneration. Method of Cajal. 

(By Dr. Bravetta.) 

intense chromatolysis. Bravetta, of Mombello, showed me slides 
with an increase in the neuroglia elements, and others with 
sclerosed and isolated masses of gray matter, indicating the chronic 
nature of the process in the cord. Bravetta showed pigmentation 
and degeneration in cells in the spinal ganglion. Spiller found 
the capsules of the cells in the ganglia in the lumbar region showed 
much proliferation of the lining cells, and, like Bravetta, the nerve 
cells presented a marked degeneration. The Nissl granules also 
disappear in some of the cells of the medulla, and there occurs in 
such cells a yellow pigmentation. (Bravetta.) Pigmentation, 



NERVOUS SYSTEM IN PELLAGRA. 



147 



swelling of the body of the cell, disappearance of the dendrites, 
chromatolysis, and displacement of the nucleus peripherally sum- 
marize the changes in the gray matter. 

Dejerine reported a case with degeneration in the nerves on the 
back cf the hand, but the patient was a chronic alcoholic instead of 
a pellagrin. In general, it may be stated that the peripheral nerves 
are normal, Bravetta in all his researches found the nerve fibers 




Fig. 39. — Chromatolysis and pigmentary degeneration in cells of the cord. Method of 

Nissl. (By Dr. Bravetta.) 



WW* 




^ 



> 



Fig. 40. — Same cr.se as shown in Fig. 39. Chromatolysis and pigmentary degeneration in 
ceils of the cord. Method of Nissl. (By Dr. Bravetta.) 



intact. Spiller studied the sciatic nerve and found the nerve fibers 
normal, but the connective tissue of the nerve and the intima of 
the vessels were proliferated. Whatever sensory changes exist in 
pellagra find their cause in the spinal ganglia and the cord, and 
not in the nerves, as in an ordinary neuritis. The process in the 
cord is chronic. The Marchi method often shows in the posterior 
column sclerosis, but no degeneration. Six out of eight of Tuc- 



148 



PELLAGRA. 



zek 7 s cases showed the sclerosis chiefly in the dorsal region, and 
this may account for the pain in the back so often complained of 
by pellagrins. The chief anatomical lesions in the cord are the 
degenerations in the posterior column and in the direct pyramidal 








Pig. 41. — Cells from the cord, showing yellow pigmentation and degeneration. Method 

of Donaggio. (By Dr. Bravetta.) 




Fig. 42. — Same case as shown in Fig. 41. Cells from the cord, showing yellow pigmen- 
tation and degeneration. Method of Donaggio. (By Dr. Bravetta.) 

tract in the lateral column. This distribution of degenerative 
changes resembles ataxic paraplegia, but in the latter the cellular 
changes in the horns and the menin go-myelitis is absent. 

The tissue changes in the cord are important, viewed both from 
their relation to clinical symptoms and to the ultimate cause of 



NERVOUS SYSTEM IN PELLAGRA, 



149 



pellagra. Mayr in Hebra *s work says : ' ' The science of patholog- 
ical anatomy has as yet contributed nothing toward the explana- 
tion of this mysterious malady." Spiller has commented on this 
point more fully than any other authority in nerve pathology, and 
it is well to note carefully his conclusions. 

"It is evident from the brief abstracts of the foreign repre- 
sentative papers treating of the pathology of pellagra that there 




Fig. 43. — Spinal cord. The cellular body is entirely invaded by vellow globular pig- 
ment, and passed through by few thin fibrils, which form a net. Neurofibrillar 
method by Donaggio. (By Dr. Bravetta.) 




Fig. 44. — Spinal cord. The cell is partially invaded by yellow globular pigment. De- 
generation of the nucleolus, perinuclear membrane, and long fibrils. Xeuro-fibrillar 
method by Donaggio. (By Dr. Bravetta.) 



is a difference of opinion in regard to the systemic or nonsystemic 
appearance of the degeneration in the spinal cord. This is a mat- 
ter of some importance, as a toxic degeneration is more likely to 
be nonsystemic. In the two cases I have studied the degeneration 
was diffuse. Indeed, from my own experience I have come to be- 
lieve that, with the exception of Friedrich's ataxia, there are few 
disorders causing a truly combined systemic disease of the spinal 
cord. The degeneration observed in anemia is not systemic, but 



150 



PELLAGRA, 




NERVOUS SYSTEM IN PELLAGRA. 151 

in the cases I have studied (quite a large number) it has invariably 
been a diffuse process. It is more intense than I have observed in 
pellagra, but not of an essentially different character. The nerve 
cells, however, are much more affected in pellagra than in anemia. 
"Writers seem to agree as to the pronounced degenerative 
changes in the cells of the anterior horns of the spinal cord and of 
the cortex of the cerebral hemispheres in pellagra. It appears from 
the first case reported in our paper that the moderate degeneration 
of the pyramidal tracts predominate clinically over the apparently 
more intense alteration of the cells of the anterior horns, so that 
exaggeration of the patellar reflexes was present. 




Fig. 47. — Spinal cord. Pigmentary granular degeneration. Method of Cajal. (By Dr. 

Bravetta.) 

"The view has been expressed (Long) that the thickening of 
bone about the intervertebral foramina, possibly more in the 
cervical region, may be a cause of the symptoms. Unfortunately, 
only the extreme lower part of the cord in the cervical region 
in case 1 was obtained, but posterior and anterior roots from 
this region, cut separately, show no distinct degeneration, even 
by the Marchi stain. Had these roots been implicated in the 
intervertebral thickening, degeneration would have been detected 
in them. I have found no indication of root degeneration in the 
thoracic or lumbo-sacral region, and the alteration of the posterior 
columns, at least below the eighth cervical segment, is clearly en- 
dogenous, as it is also m the piece of thoracic cord obtained in the 
second case. 



152 



PELLAGRA. 



"I must conclude, so far as a study of these two cases permits, 
that pellagra does not always produce — if, indeed, it ever does pro- 
duce — a truly systemic disease of the central nervous system, but 
that the degeneration is caused by some toxic or infectious sub- 
stance affecting all parts of the cerebrospinal axis, producing 
cellular degeneration and diffuse degeneration of nerve fibers in 




Fig. 48. — Spinal ganglia ; outlines irregular, 
net. Method of Cajal. 



Invasion of the special net or Marinesco's 
(By Dr. Bravetta.) 






the posterior and antero-lateral columns. It is not difficult to ex- 
plain the mental symptoms when cortical degeneration is so intense 
as may occur in pellagra, and as is seen in the brain I have studied ; 
and the insanity in this disease seems to be of a toxic or infectious 
character. ' ' 



RELATION OF CORD LESIONS AND CLINICAL SYMPTOMS. 

The most striking summary of these changes is given in Hyde's 
article on Dr. Bassoe's work. I have used this classification as a 
working basis in pellagra cases, and find it admirable. There are 
three types of cord lesions, considered clinically and related to the 
cord tracts chiefly affected. I give Hyde 's account : 

(a) Probable Pyramidal Tract Degeneration — Case 1. — Demented male epi- 
leptic, aged 37 years, admitted April, 1902, previously at a poor farm and 
another state hospital. Insane for nineteen years. Diarrhea and erythema 
of the hands during the past summer. The hospital record mentions in- 
creased tendon reflexes and positive Babinski sign on August 31, 1909. Ex- 
amination on October 10th revealed increase of all tendon reflexes without 



NERVOUS SYSTEM IN PELLAGRA. 



153 



clonus; inconstant Babinski and Oppenheim signs; pupils react to light. 
There is a slight swaying in Romberg's position, but the patient walks well 
and the heel-knee test is as good as can be expected in a demented subject. 
A note was made on October 31st that he had had stomatitis and diarrhea 
for several weeks, and lost forty pounds in weight. 




Fig. 49. — Spinal cord. Thickening and concentration of the neuro-fibrillar net. Nucleo- 
lus enlarged and irregular. Method of Cajal. (By Dr. Bravetta.) 



(b) Posterior Column Degeneration — Case 2. — An elderly demented woman 
developed characteristic skin lesions in August, 1909. Ataxia is so marked 
that she can not walk or stand alone. The wrist, elbow, knee, and ankle 
reflexes are lost. No Babinski sign. Xo involuntaries. Pupils normal. 
Characteristic erythema of the hands and face when examined on October 10th. 

(c) Combined Degeneration — Case 3. — A woman, aged 50 years, was ad- 
mitted in November, 1908, with a history of having been insane for fourteen 
months. On admission she was fairly well nourished and the tendon reflexes 






154 PELLAGRA. 

were normal. The psychosis was melancholia of involution. On August 27th 
the wrist and elbow reflexes were recorded as normal; the knee reflexes as 
increased. No Babinski sign at that time. On October 10th she was ema- 
ciated, with severe stomatitis and diarrhea. The wrist jerks and the left 
elbow jerks were absent; the right elbow jerk, weak. Knee and ankle jerks 
absent. Inconstant Babinski sign on the right side; normal flexor response 
on the left side. The pupils react rather sluggishly to light. She died on 
the following day. No necropsy. It seems probable that the pyramidal tracts 
were first involved, causing increased knee reflexes. Later, the posterior col- 
umns degenerated sufficiently to abolish nearly all of the tendon reflexes. 

Sympathetic Nervous System. 

The study of the sympathetic system has been done by R. Brugia, of 
Bologna, and summarized by Antonini. 

1. In all insane pellagrins the sympathetic nervous system is injured 
and the changes are extensive in all its component parts. 

2. The ganglia of the cervical region and the abdomen are affected differ- 
ently, according to the extent of the common forms of the pellagrous psychoses 
or of acute pellagra. 

3. In the prevailing forms there is hyperplasia of the connective tissue, 
with sclerosis, a constriction of the vessels, a reduction in the number of nerve 
cells with atrophy, and a pigmentation plainly visible; in these at times 
there is a form of hypertrophic degeneration. 

4. In the acute relightings of the pellagrous process the particular ele- 
ments present entirely different appearances. Only rarely is atrophy seen. 
Instead there occurs a turbid swelling of the cytoplasm, a central and periph- 
eral chromatolysis, complete absence of the chromatic granules, and a variety 
of lesions in the nucleus and the nucleolus ; in the supporting tissues a diffuse 
infiltration with leukocytes, a proliferation of endothelium and the formation 
of capillaries, circumscribed hemorrhages, points, and areas of softening. 

5. In every case, and more particularly in the chronic forms, the lesions 
are greater in the abdominal ganglia, both centrally and cortically. 

6. With the degeneration of the abdominal sympathetic there occurs 
acetonuria and the paretic diarrhea so frequent in insane pellagrins; while 
the lesions of the cervical sympathetic contribute in great part to cause the 
characteristic erythema, with the habitual dryness of the skin and the changes 
in the pupils. 

The conclusions in the last paragraph require further investiga- 
tion for their confirmation. The extent of the part played by the 
sympathetic system in pellagra is not yet determined. 

CEREBROSPINAL FLUID. 

1 am indebted to Dr. S. S. Hindman, pathologist to the Georgia 
State Asylum, for permission to use the results of his work on the 
spinal fluid in pellagrins. These patients came from the wards 



NERVOUS SYSTEM IN PELLAGRA. 



155 



of Dr. W. J. Cranston, who did all the punctures, and the work 
was done under the direction of Dr. E. M. Green, clinical director. 
The table on page 156 shows the results of these counts in detail 
and the averages at the foot of each column. Chemically the fluid 
is acid in reaction, twenty-three of the twenty-five cases are positive 
to the butyric acid test, and all of the twenty-four specimens tested 




Fig. 50. — Spinal ganglia. Changes in the fibrillar net : changes in the nucleus. One may 
see the different phases of degeneration in the cell. Only one cell normal. Neuro- 
fibrillar method of Donaggio. (By Dr. Bravetta.) 



reduce the copper sulphate solution. The average number of cells 
to the cubic millimeter is 35, and the percent of the cells in a 
differential count follows. 

In four cases taken in the intermission period between attacks 
Hindman found the total cell counts at 30, 17.7, 6.6, and 4. This 
is quite a decrease as compared with an average count of 35 during 
the outbreak of the attack. Further, in two of these four cases 



156 



PELLAGRA. 



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NERVOUS SYSTEM IN PELLAGRA. 



157 



the butyric acid test was only very weakly positive, and in the 
other two it was actually negative. 

Comparing Hindman's table with the results obtained in other 
diseases, excess of lymphocytes is present in syphilitic meningitis 
and syphilitic disease of the nervous system, in tabes and general 
paresis. Purves Stewart found in fifteen tabetics the average count 




Pig. 51. — Spinal cord. Increase in the neuroglia in crossed pyramidal tract. Weigert's 

method. (By Dr. Bravetta. ) 

per cubic centimeter was 125 cells. In tabes and general paresis 
the spinal fluid often reacts positively to the butyric acid test. In 
meningitis there is an excess of the polynuclear cells, except in the 
later stages, when the lymphocytes may be increased as compared 
with the early stages. In a case of syphilitic meningitis reported 
by Batten in Allbutt's System the lymphocyte count was 92 



158 PELLAGRA. 

percent. In tubercular meningitis there is often a lymphocytosis. 
The spinal fluid in pellagra is evidence that the pellagrous process 
includes in its advance organic changes in the nervous system, and 
that in general these changes are part of a chronic disease, as evi- 
denced by the association of the lymphocytes, whereas acute organic 
diseases of the nervous system are associated with an increase in the 
polynuclear elements. In pellagra the lymphocytes are increased 
both in the blood and in the cerebrospinal fluid. 



* • <h 







c 



ec<j / 



- © © 



\ 



Fig. 52. — Spinal cord. Section of Burdach's tract, showing several fibers and primary 
degeneration. Method of Donaggio. (By Dr. Bravetta.) 

This condition in pellagra is so important in view of further 
researches that I give in full Dr. Hindman's description of his 
technic and references, which may be of service to other workers. 

Examination of Cerebrospinal Fluid — Microscopical and 

Chemical. 

By Dr. S. S. Hindman, Georgia State Asylum. 

Technic used was similar to that of Fuchs and Rosenthal and as modified 
by other workers. i 

The first 4 or 5 cubic centimeters of fluid are collected in a sharp-pointed 
centrifuge tube, and subsequently used for drop or smear method in making 
differential count. 



1 Bybee and Lorenz: Report of Fifty Examinations of Cerebrospinal Fluid, with 
Special Reference to the Cell Count, Archives of Internal Medicine, January, 1911; 
Bulletins Nos. 1, 2, 3, Government Hospital for Insane, Washington, D. C, 1909, 1910, 
1911; F. J. Farnell: "The Cerebrospinal Fluid and Its Cellular Elements and Globulin 
Content," American Journal Insanity, vol. 68, No. 1, July, 1911; J. V. May (1911): 
Report of Binghamton State Hospital, New York. 



NERVOUS SYSTEM IN PELLAGRA. 159 

The second 1 or 2 cubic centimeters are collected in a small test tube, and 
used as soon as possible for chamber method for total cell count per cubic 
millimeter. To that part collected in a small test tube was added 1 or 2 
drops (from capillary pipette) of Fuchs-Rosenthal stain, which consists of 

Methyl violet 0.1 

Glacial acetic acid 2.0 

Distilled water 50.0 

Filter and use. 

The tube is shaken thoroughly and allowed to stand for five or ten minutes 
in order to stain all of the cells present (red cells, if present, do not take 
the stain in such short time). A few drops are withdrawn from the tube 










4. 



« 






, °-% to 



r *« 



Fig. 53. — Spinal cord. Section of Burdach's tract, showing numerous fibers in secondary 
degeneration. Marchi's method. (By Dr. Bravetta.) 

by means of a freshly made capillary pipette, and, after allowing 2 or 3 
drops to escape, 1 drop is placed in the counting chamber of a hemacytometer 
(Zappert's ruling), cover glass adjusted, and slide is allowed to stand on 
the stage of the microscope for at least fifteen minutes before counting to 
allow all cells to settle upon ruled surface. 

The number of cells in the entire ruled surface of nine large squares are 
counted. Divide the result by nine for average of one, and multiply by ten 
(one-tenth required depth in one layer), and you have the number of cells 
per cubic millimeter. As the addition of 1 or 2 drops of stain to 2 cubic 
centimeters of fluid reduces the dilution to a minimum, it is not necessary to 
use the white cell pipette as recommended by many workers. In fact, some 
authorities, in using the pipette, by drawing in 1 part stain to 100 parts of 
fluid and shaking, etc., have entirely disregarded the dilution in their cal- 
culation. One drop of stain from a capillary pipette added to 3 cubic centi- 



160 PELLAGRA. 

meters of fluid and shaken thoroughly will stain all lymphocytes and other 
elements sufficiently well for the count, and give practically no appreciable 
error. The important point to observe is to make the count as soon after 
puncture as possible, owing to the tendency of the cells to settle to the bot- 
tom. 

As to the degeneration of cells on standing, this in our experience does 
not occur nearly so quickly as some have stated. A larger counting chamber, 
with a larger ruled surface and greater depth, has been used extensively by 
others, which is necessarily more accurate for cases showing only a slight 
increase in cellular elements. In these cases here reported at least two sepa- 
rate counts were made in each case and an average taken for final result. 

That part of fluid collected in centrifuge tubes was swung at the rate of 
2,500 or 3,000 revolutions per minute for thirty minutes in an electrically 
driven centrifuge; supernatant fluid poured off and tubes allowed to thor- 
oughly drain; sediment is then taken up with freshly made hair pipette and 
deposited in not less than 2 drops on newly cleaned slide, spreading out sedi- 
ment so it will cover approximately a surface one-half centimeter in diameter. 
Smears are allowed to dry in the air, fixed with absolute methyl alcohol for 
one to two minutes, and stained with Delafield's hematoxylin and eosin, allow- 
ing three to five minutes for former and one to two minutes for the eosin. 
Any excess of stain can readily be removed by passing through 95 percent 
alcohol, etc., as staining tissues. 

The slides are examined under an oil immersion lens, and a rough differ- 
entiation of cells made from counting at least 300 cells. 

Lymphocytes are generally in excess and are easily seen, and appear as 
small dark cells (or nuclei, with little or no protoplasm), varying in size 
from a little less to a little larger than the size of a red blood cell. For more 
complete description see Bybee-Lorenz and other references mentioned above. 
This type of cell is generally agreed upon and can not be easily mistaken for 
any other. 

Polymorphonuclear elements present considerable variation in their char- 
acteristics, and some are not very definite; for the most part, they resemble 
more or less the same type found in the blood, but show different divisions 
of nuclei, and are usually smaller and stain differently. "The protoplasm 
of the larger cells usually is very faintly pink, while the smaller types stain 
a deeper rose color." (Bybee and Lorenz in their original article.) 

Plasma cells, as described by Bybee and Lorenz, vary in size from a little 
less than a red cell to two and rarely three times their size. Nucleus is 
darkly staining, but does not approach the inky blackness of the small lym- 
phocyte. ( For complete description see original article of Bybee and Lorenz. ) 

Endothelial cells in these cases include all of that variety, but it should 
be mentioned that the ordinary endothelial cell and that type coming from 
the spinal canal proper are usually quite different. (See Hough, Government 
Hospital for the Insane, Bulletins 1, 2, 3.) 

Unknown and degenerated cells need no description. 

Other authorities describe as many as six or seven types of cells in cerebro- 
spinal fluid, and Hough, using the Alzheimer method of examination, reports 
eight to ten different types, with as many varieties for each type. The small 






i 



NERVOUS SYSTEM IN PELLAGRA. 161 

lymphocyte is, however, recognized as the same by all, and, since about five 
cells per cubic millimeter are recognized as normal and the larger percentage 
of cells found here are of this type, it clearly indicates that there is an in- 
creased lymphocytosis in the cerebrospinal fluid of pellagrins. We are now 
studying other cases, and hope to have in the near future at least 150 or 200 
cases to report upon. 

All authorities concede that the differential count is more or less variable, 
depending upon each worker's idea of the different cell types. W. H. Hough, 
Bulletin No. 2, Government Hospital for the Insane; F. W. Mott, Lancet 
(London), July 29, 1910; and J. V. May, Binghamton, State Hospital Re- 
port, point out that a positive butyric acid reaction as originally suggested 
by Noguehi (Serum Diagnosis of Syphilis, first and second edition, 1910, 
1911) is not specific for any one disease. We can confirm this, as in all 
cases of pellagra and also in others examined we have obtained an increase 
in the globulin content^ as evidenced by a flocculent precipitate, often heating 0.2 
cubic centimeters spinal fluid with 0.5 cubic centimeters of 10-percent solution 
pure butyric acid in normal (0.9-percent) saline solution, adding 0.1 cubic 
centimeters normal sodium hydrate and reheating. Precipitates of varying 
degrees occur from a few flocculent particles to a dense one which covers 
the bottom of the tube after settling. The butyric acid test is, however, to a 
certain extent a control on the microscopical findings, as those specimens with 
a low cell count invariably show weak butyric acid reaction. 

All specimens examined were alkaline in reaction, and reduced CuSo4 in 
alkaline solution. Benedict's one solution reagent was used for testing re- 
duction of CuSol, as we believe, after comparisons with Fehling's, it is more 
reliable and also saves considerable time. To 1 or 2 cubic centimeters of 
this reagent about 0.3 cubic centimeter fluid were added and mixture heated 
for one-half to one minute, when a yellow or reddish yellow precipitate oc- 
curred. 

PAIN. 

The pains in pellagra resemble to a degree the pains of neuras- 
thenia. These pains are variable and transient, like the pains so 
often complained of by a chronic neurasthenic. They are more 
common during the attack in the initial stage and during the whole 
of the second or neurasthenic stage. They are most common in the 
back, and resemble those cases of painful spine following railway 
accidents and other injuries in a traumatic neurasthenic. Tender- 
ness may occur rarely the Avhole length of the spine, but usually it 
is more common in the dorsal region, and the tenderness is often 
greater on one side. Sandwith, in 178 cases, found pain absent in 
59, pain in the whole back in 42, pain between the first and fourth 
dorsal vertebra in 12, between the fifth and eighth dorsal in 35, be- 
tween the ninth and twelfth in 17, and 13 had pain in the lumbar 
region. In only 19 of the whole number was the pain symmetrical. 



162 PELLAGRA. 

In Egypt the back pains occur in about one-third the cases, and 
is a symptom that disappears. This pain may vary from tender- 
ness on pressure to an actual hurt on walking, rising, or sitting. 
The pains may radiate down into the hips, though actual coccygo- 
dynia is rare. Siler found spinal tenderness present in 14 of the 
Illinois asylum cases. In Italy commonly and in America more 
rarely the pain is so severe as to cause the pellagrin to walk bent 
over and with his spine held rather stiffly to reduce the pain. I 
saw one negress recently between attacks and apparently in good 
physical condition, yet the pain in the back persisted and the walk 
was stooped and careful. The tenderness elicited on pressure is to 
one or the other side of the spinous processes. (Watson.) 

These pains are by no means confined to the back, but may even 
be absent in the back and occur elsewhere. Headache occurs, but 
it is more common in the early onset and is not usually severe. 
The burning pains have been discussed in the chapters on the 
Alimentary Tract and the Skin. They occur more often in the 
extremities and the stomach, but are occasionally more widely dis- 
tributed. Gastralgia has also been referred to. Pains are occa- 
sionally complained of in the hips and feet, and there may be a 
general hyperesthesia, with pains and soreness "all over," as in 
influenza. Pains in the joints are rare. 

REFLEXES. 

Exaggerated knee jerks characterize pellagra in its early stages. 
There are exceptions to this rule in late cases, and occasionally in 
those of Hyde's type B, with posterior tract degeneration to a 
marked degree. In private practice, in cases preceding insanity 
and without a severe involvement of the cord, the knee jerk is prac- 
tically always increased. It is often pronounced, like the knee jerk 
in hysteria in a young woman. The slightest tap of the tendon 
will cause a pronounced response, and with repeated taps the re- 
sponses are so exaggerated that the leg is kept nearly extended and 
the foot in the air. In early cases the exaggerated knee jerks and 
the exaggeration of other reflexes, like the elbow, are due in large 
measure to the neurasthenic condition of the patient, the blow his 
vitality has received from the disease, and the hypersensitive con- 
dition of the nervous system. Later the organic tissue changes 
occur in the cord; confined to the posterior column, the reflexes 



NERVOUS SYSTEM IX PELLAGRA. 163 

are diminished or absent, analogous to locomotor ataxia ; confined 
chiefly to the direct pyramidal tracts, the reflexes are exaggerated, 
analogous to ataxic paraplegia and the escape of the posterior root 
zones in that disease ; with the involvement of the posterior columns 
and the lateral columns, the reflexes are at first increased, and later 
may decrease or be absent. This last condition is similar to the 
subacute degeneration of the cord or diffuse degeneration of the 
cord as described by Putnam, and in which there is persistent 
parasthesia, weakness, rigidity, and j^ain in the back. 

In the early stages of the disease these knee jerks are exag- 
gerated more during the attack and less in the intermission. A 
knee jerk may be increased during the attack and then return 
to normal as the attack recedes. This is shown very well by Sand- 
with's comparative figures. In 165 cases studied during their hos- 
pital stay, only 3 had normal jerks, increased in 48, extremely 
increased in 76, diminished in 15, and absent in 23. After treat- 
ment and improvement at the hospital, 129 of his cases showed 
normal knee jerks in 10 percent, slightly increased in 51 percent, 
extremely increased in 10 percent, decreased in 12 percent, and 
absent in 8 percent. Siler's cases among the insane showed knee 
jerks normal in 20 percent, increased in 62 percent, and decreased 
or absent in 18 percent. Occasionally the jerks vary on the two 
sides. Tucker reports a case of this kind, and I saw one such case 
in Italy. Tucker had increased reflexes in 10 out of 46 cases. 

Ankle clonus is rare, and present only in advanced and incurable 
cases. It is more frequently seen in the asylums than in private 
practice, and is often asymmetrical. The asymmetry follows the 
asymmetry in the patellar reflex, changes in the elbow reflex, the 
Babinski reflex, and the reflexes of the skin. The Babinski is more 
common than the ankle clonus, and in turn may be asymmetrical, 
present on one side and absent on the other, or more exaggerated 
on one side than on the other. It is found chiefly in the insane, 
the advanced, and in the acute and cachectic forms. Siler tested 
this in the Illinois cases and found the plantar reflex normal in 32 
percent, increased in 53 percent, and diminished in 15 percent. The 
skin reflexes show variation in elevation or absence. The pharyn- 
geal reflex is usually decreased. In general it may be said that 
the knee jerk is the most important and the elbow reflex usually 
follows the knee type. With knee jerk, Babinski, and clonus the 
case is advanced and serious. The early presence of the knee jerk 



164 PELLAGRA. 

and its gradual disappearance indicates increasing changes in the 
cord. 

CHANGES IN THE MUSCULAR SYSTEM. 

In about half the cases of pellagra the muscles show atrophy, 
and occasionally fatty degeneration. There is a greater percentage 
of asylum cases with pronounced muscular atrophy than in cases 
seen in private practice. Out of 44 cases, Lombroso found atrophy 
in the muscles in 21. The muscles are pale from lack of blood, 
and the entire muscular system is in a state of malnutrition, lacking 
the vivid vitality and strength of normal muscle. It is evident 
that muscular weakness is the natural result of these changes, and, 
with the progress of the disease and the rather sedentary life of 
the advanced cases, the atrophy and weakness tend always to in- 
crease. Even in those cases without atrophy the muscular strength 
is decreased, and the inability to keep pace with the healthy is 
apparent. This weakness of the muscles attacks preferably the 
lower extremities, and in the upper extremities shows a selective 
action for the extensors, with resulting overaction of the flexors and 
accompanying contractures. The extensors get into a state of 
paresis, so that the limbs are in a state of semiflexion owing to a 
preponderance of the flexors, and remain fixed or resistant when 
an attempt is made to move them. (Hirsch.) 

Tucker's cases show muscular atrophy in 35 out of 52 cases, and 
muscular weakness in 49 out of 53 cases. The electrical excitability 
of the muscles is very little changed, though the flexors of the fore- 
arms are more easily excited than the extensors. Reaction of de- 
generation is usually absent. The greater excitability of the 
flexors is explained by the paretic tendency of the extensors, which 
leads to contractures in the hand. On mechanical stimulation, in- 
complete muscular contractures and fibrillary twitchings occur, 
indicating the weakness both of the muscles and the centers of the 
innervation. This response to mechanical stimulation is evidently 
due to the irritation of the peripheral nerves from the circulating 
toxin, analogous to the marked and incomplete contraction of the 
biceps in typhoid fever, according to the recent test noted by Burke, 
of Iowa, though this condition is really a nodular myoidema. 

"With this atrophy or muscular weakness gradually progressive 
as the disease advances, and the ever-increasing organic changes 
in the cord and brain, tremors, cramps, contractures, uncertain 



NERVOUS SYSTEM IN PELLAGRA. 165 

and painful gait, rigidity of certain groups, with stiffness of ad- 
jacent joints, develop with great variability in different cases. 
Tremor is more common during the attack, and in advanced cases 
accompanied by a pellagrous psychosis. It may occur rarely all 
over the body, but is usually more common in the upper half of 
the body and there more often in the hands ; then the tongue, lips, 
and face in order. According to Cabot, tremor is a clonic spasm 
of short duration, and its cause here is the toxemia, weakness, and 
neurasthenia. It is best seen, when present, by asking the patient 
to put out his tongue as far as possible or extending the hand with 
the fingers wide apart. I have seen the facial muscles exhibit 
tremors in pellagrins, one clonic contraction following another 
rapidly. Such a condition is more common during the acme of the 
attack. After exercise in pellagrins, even between attacks, these 
tremors are accentuated, especially when great weakness is present. 

A cramp is a local spasm of a muscle or a muscle group — a kind 
of epilepsy of a muscle. It occurs often during sleep, and more 
frequently during the night, when the conscious control of the mind 
is absent. It characterizes neurasthenia and states of chronic ex- 
haustion. In pellagrins it is common. Tucker's admirable ques- 
tions on this point gave cramps in 28 out of 52 cases; in 9 they 
were in the abdomen, and in the other cases in the arms, hands, 
legs, back, and in 3 cases they were general. 

After several attacks, or occasionally after one attack, as in 
Elrod's case, the muscles lose their elastic tone and become rigid, 
with accompanying stiffness of the joints covered. These contrac- 
tures concern chiefly the flexors of the arms and legs. Fig. 62 
shows the permanent contraction of the little and ring fingers of 
the left hand following one severe attack in the spring. These 
fingers were flexed on account of the paresis of the extensors, and 
were extended only slowly and with difficulty. The thumb may 
be contracted across the palm, or the arms carried drawn up. In 
these advanced cases one is often struck by the stiffness of the legs 
when the patient sits and when an attempt is made to relax the 
lower extremity. The foot is held half extended and the leg stiff, 
like in a spastic paraplegia. This rigidity of the muscles is pro- 
nounced during an attack, especially in a cachectic condition. The 
pellagrin lies in bed with the feet drawn up and the thighs flexed 
on the abdomen. In one case this position was maintained for a 
month. Here, too, the foot is often flexed and the ankle joint is 



166 PELLAGRA. 

stiff, and the foot moves with difficulty. The pellagrin in this con- 
dition is unable to quickly relax the flexor muscles. 

"With muscular atrophy and weakness, stiffness of the joints, 
spinal tenderness, and rigidity, the natural walk is changed. This 
is true only of the advanced cases with pronounced cord changes, 
emaciation, paretic conditions, or marked weakness of the entire 
body. In the vast majority of pellagrins the walk is natural and 
easy, and especially is this true the greater part of the year between 
the attacks. Even as the disease advances, the only variation from 
the normal walk is an increased slowness and a slight stooping 
of the shoulders. In the advanced cases, with changed walk, there 
is a combination in the different cases of slowness, ataxia, spastic 
walk, and simple weakness. These vary according to the condi- 
tion of the pellagrin and the tracts of the cord chiefly affected. 
As a rule, the paretic gait is in evidence. The legs are kept well 
apart, the shoulders raised and bent forward, the body inclined 
more to one side than the other, and falling is so easy that a staff 
is necessary. The patient rises with care, and the first few steps 
are taken slowly and as if the feet were hunting for the ground. 
Vertigo adds to this fear of falling, and the patient "must get 
started right" before he walks even easily. The feet are kept 
farther apart than normally, and put down with care. The knees 
are more flexed than usual, and the legs lack the natural swing of 
health and vigor. Following paralysis, the gait becomes hemiplegic, 
and occasionally there is a tendency to fall forward or backward. 

Paralysis occurs, but it is not common, and is seen chiefly in 
advanced cases in the asylums. Preceding death, meningeal symp- 
toms develop in a few cases, with tetanic and choreic movements, 
epileptiform attacks, and even an occasional convulsion. Kernig's 
sign may be present in such cases, with clonus and spasticity. 
During the convulsive seizures or the meningeal rigidity the pupils 
are apt to be irregular and act independently one of the other, or 
with external or internal deviation. At this time wrist drop is 
seen, paralysis of the sphincters, with incontinence of the urine 
and feces, and delirium. Bedsores are rare. 

Insomnia is a prodromal sign which characterizes many cases 
in the period of onset of the attack, and the insomnia in such cases 
is increased during the outbreak. As the disease progresses and 
neurasthenia develops, sadness, silence, and sleeplessness increase. 
The voice changes from the natural, modulated human voice to 



NERVOUS SYSTEM IN PELLAGRA. 



167 



an undertone of monotony and sadness. It is a monotone on a low 
level. In this neurasthenic stage the pellagrin talks very little, 
and often one of the first complaints heard in the morning is the 
lack of sleep the previous night. His nervous condition is attrib- 
uted to the inability to sleep, and the physician is told, "If I 
could only sleep, I would be all right." Sandwith observed sleep 




Fig. 54. — Pellagrous insanity. Dermatitis on hand, with, exfoliation of the skin. 

tesy of Dr. Bravetta.) 



(Cour- 



in 150 pellagrins ; 40 percent of them slept normally, 23 percent six 
hours, 19 percent four hours, and 18 percent less than three hours 
in the twenty-four. This is in Egypt, where the nervous phenom- 
ena are not as pronounced as in Italy or America. All of my 
cases have complained of insomnia at times, and of "just lying 
awake" during the night. 

At first the mental condition is not affected, and after one or 



168 PELLAGRA. 

two annual attacks, or indeed after several mild attacks, with the 
patient still in the initial degree of the disease, the mental condi- 
tion remains normal, the spirits cheerful, and the mind may main- 
tain its normal vigor. With the progress of the chronic form, or 
the rapid advance of the acute and subchronic cachectic forms, 
the mental processes become retarded. The transient headaches 
of the beginning are gone, and instead dizziness, noises in the 
ears, neurasthenic sensations of weight, lightness, and distinct pul- 
sations increase the introspective wondering of the pellagrous 
neurasthenic. The causes of these varied symptoms in the head 
are not so clear. The whole brain in pellagra is in a state of 
malnutrition, and this is accentuated as time goes on, both by the 
increasing organic changes taking place in the brain and the cord, 
and by the inability of the whole system to gain from the food 
the desired fuel and substances for repair. These ingredients are 
in the food, but the poison of pellagra prevents the system from 
taking advantage of them. Pellagra places in the nerve cell a 
poison of some kind, and takes from the nerve cell its power of self- 
nutrition. In short, pellagra exhausts the nervous system. 

The vertigo, noises, and roaring in the ears are causally related 
to each other. The basic cause is the lack of ability of the brain 
to overcome the poison and to nourish itself. Added to this are 
the changes in the cortical and the cerebellar cells. The exhaus- 
tion of the whole brain, or cerebrasthenia, can of itself cause these 
symptoms. As pointed out by Beard, in exhaustion of the brain 
there often occurs a hyperesthesia of the auditory nerve like the 
hyperesthesia of the optic nerve in the same disease, both of which 
are inconstant, variable, and capricious, and that without organic 
tissue changes in the auditory nerve. Vertigo can result "from 
affection of the higher cerebral centers, or of the coordinating 
cerebellar centers, or from affection of any of the afferent paths, 
as from the semicircular canals. (Purves Stewart.) In advanced 
cases the ataxia may be due to the cerebellar changes, but earlier 
in the disease the vertigo and noises in the ears are more to be 
accounted for as neurasthenic symptoms than otherwise. Indeed, 
the noises in the ears are often complained of as a prodromal 
symptom developing before the dermatitis. I have found no re- 
port of any tissue changes in the auditory ganglia or in the audi- 
tory nerve, but a research in this locality might throw additional 
light on these symptoms. 



NERVOUS SYSTEM IN PELLAGRA. 



169 



Neurasthenia is the vitiated soil that spreads over the body as 
it takes the down trail of emaciation and weakness. These re- 
curring attacks of dyspepsia and indigestion, of oral rawness and 
rectal soreness, these diarrheas that come in the spring, leave 
stretches of bareness in the nervous system, both in respect to the 
vigor of the mind and the organic wholeness of the nerve tissue. 




Fig. 55. — Pellagrous insanity. Dermatitis on hands. Period of recession. Note expres- 
sion on face. (Courtesy of Dr. Bravetta.) 

These recurring involvements of the abdominal ganglia of the 
sympathetic system make their impress on the mind, and the pel- 
lagrin becomes conscious of all his abdominal organs. The pel- 
lagrous neurasthenia begets introspection, and the introspection 
begets hypochondria, and hypochondria begets permanent sadness. 
The smile of life has gone and the set of despair has come. Imagine 
the condition of the pellagrin as he himself views his condition. 



170 PELLAGRA. 

The complaint of this patient relates to the gradual disintegration 
of his body and of his mind. 

For one or two years, or even a few years longer, he stood his 
disease very well. Then the strange feelings in his head common 
during the attack begin to be permanent ; the head is light or full, 
dizzy sensations come, he must rise slowly lest he fall, his legs 
seem weak, and walking is slow and careful. He has been growing 
worse all these years instead of better. His hope is beginning to 
leave him — his mind goes slowly like his feet. He can no longer 
think quickly as formerly. His thoughts are few and slow, and 
he is no longer certain of himself. Like Napoleon in his last 
illness, each pellagrin begins to feel that he ' ' can no longer unbend 
the bow." He is no longer himself. Memory begins to waver, 
and the recent past is more like an impotent dream. The lines 
and letters run after each other on the page, so that he can hardly 
use his mind to read. Formications, burnings, creepy feelings, 
coldness, numbness, run over the skin. The muscles of the legs 
seem rather lifeless, and the feet lift like lead. His vision is that 
of an old man, his face is thin, and his brow wrinkled a score of 
years before its time. He fears men, and grows silent. His 
thoughts are gone, and he can no more supply his tongue with 
many words. Neurasthenia, sadness, hypochondria, edge on melan- 
choly, and the mind begins to lift its tent and steal away. 

Pellagra is a disease of the body, but in a majority of the cases 
it involves the mind to a greater or less degree. The somatic dis- 
integration usually precedes the psj^chic disintegration; but the 
more the advance of the former, the greater the give of the mind. 
Even in the neurasthenic stage, with the mind in comparatively 
good condition, on close examination there will be found: 

1. A simple retardation of the mental processes. 

2. Impairment of memory. 

3. A general feeling of depression. 

The stream of consciousness is slowed, and new ideas are in- 
corporated with great slowness, Memory is poor, and old impres- 
sions rise to the surface with difficulty, or not at all. The number 
of points of contact is decreased, and there is just mind enough 
for a very limited number of ideas. What mind there is moves 
with exceeding slowness. There is no better illustration of this 
than the inability of the pellagrin to answer easy questions. 
Jansen was impressed with this, and wrote in his Latin treatise, 



NERVOUS SYSTEM IN PELLAGRA. 171 

' ' Interrogate vix respondebant " — when asked questions, they re- 
sponded with difficulty. Furthermore, what questions they do 
answer come in monosyllables in a monotone and with hesitation. 
Even such a simple question as "When did you wake this morn- 
ing," or "How far do you live from town," seemingly causes an 
effort to comprehend or to answer. I have also noticed that what 
is answered is put in an indefinite and noncommittal way. The 
pellagrin seems totally unable to incorporate a definite idea, to 
consider that idea, and to give a definite response to the idea as 
considered. Probably his poor memory has something to do with 
this. I have seen one apparently in good mental condition, and 
well orientated to his environment, look appealingly to his brother 
on being asked how far he lived in the country, and, again, how 
long he had been sick, and yet he had just been describing his 
condition and where he lived. This illustrates his inability to as- 
sociate ideas, to form new concepts, and to sort the usual run of 
perceptions. The pellagrin loses his idea of the passage of time. 
He comes into the consulting room, sits, looks, listens, says little, 
and seems to have no idea of moving or going. Added to his 
mental inertia is his chronic depression. His dermatitis and diar- 
rhea have left this depression in their wake. The world resolves 
itself into his slowly uttered account of his own history and con- 
dition. 

PSYCHOSES ACCOMPANYING PELLAGRA. 

Dr. E. M. Green, clinical director of the Georgia Asylum for 
the Insane at Milledgeville, has given me the facts and cases on 
the psychoses accompanying pellagra, which follow: 

From January 1 to November 1, 1911, there were admitted to 
this asylum 60 cases which presented evidence of pellagra on ad- 
mission. The mental condition as well as the physical condition 
of these were studied in detail by Dr. Green and his corps of staff 
physicians, and the resulting facts grouped and related by Dr. 
Green. It is well to present these in the form of summaries, and 
to give an illustration of each of the types as classified. 

It is estimated that about 10 percent of the pellagrins in Italy 
are insane. It is impossible to make an estimate as to the relative 
number in America on account of the inability to obtain the exact 
number either of the pellagrous or of the pellagrous insane. 1 
am disposed to think it would be far under 10 percent of the whole 



172 PELLAGRA. 

number, and that 5 percent would be nearer. There is a distinc- 
tion just here pointed out by Warnock in his 1909 report when 
he writes: "These figures refer to cases of insanity due to pel- 
lagra — not to cases showing pellagrous symptoms merely. Thus 
we admit numbers of congenital imbeciles, precocious dements, 
epileptics, and senile dements who have signs of pellagra, but their 
pellagra seems a coincident illness — not a cause of the insanity; 
so their diagnosis would appear under other headings. ' ' He ranks 
pellagra as a cause of insanity along with syphilis, alcohol, and 
hashish. It is evident, then, that (1) one may have pellagra and 
not be insane; (2) one may be insane from causes other than pel- 
lagra and later develop pellagra; (3) one may be insane with pel- 
lagra as the direct cause. This present discussion considers chiefly 
the last group. 

The physicians in the asylums of the country see pellagrins from 
the standpoint of the mind first and the body afterward; the phy- 
sicians in private practice see pellagrins from the standpoint of 
the body first and the mind afterward. The asylum physician 
meets the pellagrin with his mind gone ; the physician outside sees 
the pellagrin until the mental disintegration ensues, and, although 
the patient goes to the asylum mentally disabled, he is a pellagrin, 
with the disease still in evolution. It is well for each group of 
physicians to get the point of view of the other, and each group 
gains evidence from experience on the disease. Outside the asylum 
the disease presents many of its lesser phases; inside it presents 
the accentuated phases. There is no finer lesson in pellagra than 
to see and examine the pellagrins in the asylums, and one is at 
once compelled to enlarge his horizon of the manifold character 
and variability of the pellagrous syndrome. 

The classification of the psychoses accompanying the disease is 
important. One of two courses is open — either to add a new en- 
tity to the classification of insanity and call it pellagrous insanity, 
or, viewing pellagra merely as one of the causes of insanity, refer 
to pellagra with its accompanying psychosis, and the psychosis is 
classified according to the type which the symptoms in their sum 
total indicate. This is best stated by Dr. Green in regard to his 
own cases : 

The mental picture which these cases present is not uniform, -and I do not 
believe that at present we can recognize "pellagrous insanity" as an entity. 
Temporarily, at least, I think it best to place them under the general heading 






NERVOUS SYSTEM IN PELLAGRA. 



173 



of "psychoses accompanying pellagra," and to subdivide this group into the 
different types which the mental symptoms seem to indicate. If the mental 
symptoms are those of dementia precox, the subdivision should be "dementia 
precox type." If the mental symptoms are those of infective exhaustive 
psychosis, the subdivision should be "infective exhaustive type," and so on 
through the different types. 

There exists no combination of mental symptoms which at present we can 




Fig. 56. — Pellagrous insanity. Dry dermatitis, with exfoliation of the skin. Face sad 
and serious; brow wrinkled and puckered. (Courtesy of Dr. Bravetta.) 



recognize as being peculiar to pellagra alone. Many forms of psychosis may 
accompany this disease — the latter being the chief, possibly the sole, etiological 
factor. These cases are grouped under the general heading, "psychoses accom- 
panying pellagra," which is subdivided into types as the symptoms noted 
seem to approach those of the recognized forms of insanity. 

1. The largest of these subgroups is the "infective exhaustive type." It 
is characterized by the symptoms found in other infective exhaustive psychoses, 



174 PELLAGRAo 

and may appear as acute delirium, amentia, or chronic nervous exhaustion. 
The symptoms most commonly found in this type are clouding of the con- 
sciousness, confusion, delirium, apprehension, restlessness, and hallucinations. 

2. The next largest of the subgroups is the "dementia precox type." In 
this the patient may appear apathetic, seclusive, inattentive, negative, and 
deteriorated. Mannerisms, stereotypes, neologisms, impulsive movements, and 
cries may be noted. Delusions of persecution, poison, and influence may be 
expressed, and hallucinations are usually present. These cases may show the 
hebephrenic, katatonic, or paranoid forms observed in other cases of dementia 
precox. 

3. The "manic depressive type" is less frequently met with. It usually 
takes the depressed form, in which are observed depression, decreased psycho- 
motor activity, and difficulty in thinking. Ideas of insufficiency, sin, with 
self-reproach, and a tendency to suicide are not uncommon, while hallucina- 
tions are usually present. The manic form presents the usual manic symp- 
toms of elation, increased psychomotor activity, flight of ideas, distractibility, 
excitement, and boisterousness. 

4. In the "general paralysis type" are found the usual physical signs 
accompanying that disease. These consist of disturbance of sensation, in- 
crease or loss of deep reflexes, inequality or irregularity of the pupils, dis- 
turbed pupillary reaction to light, tremors, unsteady gait, and speech dis- 
turbances. The accompanying mental picture is usually that of dementia. 

5. The "involutional melancholia type" appears after middle life, and 
presents an agitated depression, with ideas of unworthiness, sin, and self- 
reproach. Suicidal tendencies are marked and auditory hallucinations are 
frequent. 

6. The "senile dementia" type is seen in those who have reached the 
middle period of life, and offers the usual symptoms of this condition. Here 
are found increased irritability, aimless wandering, unreasoning resistance, 
disorientation, with memory disturbance, and often accompanied by confusion 
and hallucinations. 

7. The "unclassified type" represents a large number of cases. The symp- 
toms are either indefinite, can not be elicited, or are of such character 
that they simulate no recognized form of psychosis, nor have they enough in 
common to form a separate group. 

From January 1 to November 1, 1911, Dr. Green and his staff 
studied 60 cases which presented evidence of pellagra on admission. 
These were classified according to the "type of psychosis" as fol- 
lows: 

Infective exhaustive -. 30 

Manic depressive 9 

Dementia precox 9 

General paralysis 2 

Senile 3 

Involution melancholia 2 

Unclassified . 5 

60 



NERVOUS SYSTEM IN PELLAGRA. 



175 



CASES ILLUSTRATING EACH TYPE OF PSYCHOSIS. 
Infective Exhaustive Type. 

M. J. G., white female, aged 42, married, domestic servant. Has had one 
previous attack of insanity. 




Fig. 57. — Pellagrous insanity in the aged. Face wrinkled, puckered, and drawn; hands 
cracked and dry; increase of wrinkles over finger joints. Typical expression. 
(Courtesy of Dr. Bravetta.) 



Duration of pellagra is eighteen months. The duration of insanity is 
twenty-three days. The evidences of pellagra are wrinkling and roughening 
of the skin on the back of the hands. There is abdominal tenderness, and 
eighteen months ago there was stomatitis, diarrhea, and eruption over the 



176 PELLAGRA. 

back of the hands. The only complication is an apical systolic murmur. The 
termination was death. 

The nervous symptoms were muscular strength diminished, deep reflexes 
exaggerated, pupils react sluggishly to light, sphincters not controlled, speech 
slurring, Babinski sign uncertain, and ankle clonus was not constant. 

The mental symptoms were delirium, confusion, restlessness, agitation, 
incoherence, apprehension. There were hallucinations of hearing, and dis- 
orientation for time, place, and person. Memory was poor for both recent 
and remote events. Retention was impaired, and grasp on school knowledge 
and general information was poor. Counting and calculation defective. At- 
tention can not be held. Insight lost. Judgment much impaired. 

The Manic Depressive Type. 

E. C, negro female, aged 33, widow, farm laborer. The duration of her 
pellagra is unknown, and she has been insane one month. The skin is dark- 
ened on her wrists, dorsa of her hands, and lower third of her forearms. 
There are pigmented spots on her face, chest, and back. Her tongue is red, 
and there is stomatitis and vaginitis. The labia are red, with denuded areas 
and a whitish deposit. The abdomen is rigid and there is constipation. No 
complications. 

The nervous symptoms are subjective complaints of vertigo, numbness 
of hands, and sensations as if pins were sticking into the skin. The facial 
muscles were weakened and the face drooped. The deep reflexes were exag- 
gerated and there was coarse tremor of the fingers. The tongue showed a 
fine tremor, with speech sticking and slurring. 

The mental symptoms showed depression and slowness, speech in an under- 
tone and not spontaneous. Ideas of sin present, self-reproachful, with suicidal 
tendencies. Hallucinations of sight and hearing, with a history of excite- 
ments, during which it was necessary to tie her. Orientation undisturbed 
and memory preserved. Retention defective, but counting and calculation 
good. Insight fairly good. Judgment impaired. 

Termination, death. 

Dementia Precox Type. 

S. S., negro male, aged 30, single, no occupation. Duration of his pellagra 
is unknown and his insanity has lasted six months. There is a darkening 
and roughening of the skin on the back of the hands, wrists, elbows, and feet. 
The tongue is fissured and diarrhea is present. Syphilis exists as a com- 
plication. 

The nervous symptoms are headache, muscular weakness, all deep reflexes 
exaggerated, fine tremor of tongue and fingers, and twitching of muscles about 
eyes and mouth. 

The mental symptoms are apathy, inattention, contradictory replies, 
grimaces, impulsive movements and replies, mannerisms, seclusive and not 
spontaneous. Ideas of influence, persecution, poison, neologisms. Hallucina- 
tions of sight and hearing. Orientation disturbed for time. Memory fairly 
good for both recent and remote events. Retention defective. Grasp on 



NERVOUS SYSTEA1 IN PELLAGRA. 177 

school knowledge and general information good. Counting and calculation 
good. Insight partially preserved and judgment defective. 
Termination, death. 

General Paralysis Type. 

M. R., wife of a business man, aged 48. Duration of pellagra unknown 
and insane for last three months. There is reddening of the skin over the 
knuckles, scaling of the epidermis from the elbows, and especially on the 
dorsal surface of the hands and forearms. The abdomen is full and tender 
on pressure. There are no complications. 

The nervous symptoms are muscular weakness, vertigo, temperature. 
Sense impaired in the lower extremity. Deep reflexes are exaggerated. In- 
coordination of voluntary movements. Gait careful. Tremor of tongue. Pu- 
pils irregular and somewhat sluggish to light. Speech has slight defect. 

The mental s3 7 mptoms are apathy, hallucination of sight, orientation dis- 
turbed for time. Memory is impaired both for recent and remote events. 
Retention is poor. Grasp on school knowledge is defective. Counting fairly 
good. Calculation lost. Insight absent. Judgment poor. 

Termination, still under treatment. 

Senile Dementia Type. 

K. G., laborer, aged 65 years. He has had pellagra seven months, and 
been insane two and one-half months. He has the skin lesions of pellagra 
on his knees and back of his feet, and his hands are very rough and pig- 
mented. His tongue and buccal mucosa are very red and diarrhea exists. 
There are no complications. 

The nervous symptoms show arcus senilis, muscular weakness, knee jerks 
increased. The abdominal and cremasteric reflexes are absent. The gait is 
unsteady. 

The mental symptoms show irritability. He wanders aimlessly round the 
ward, unable to find either his room or the dining-room. He is slightly resist- 
ive and demented. There is disorientation for time, place, and person. Mem- 
ory for remote events much better than for recent ones. Retention is poor. 
He counts fairly well, but can not calculate. General information fairly well 
preserved. Insight absent and judgment very defective. 

Termination, death. 

Involutional Melancholia Type. 

M. S., Avife of a farmer, aged 53. The first attack of pellagra was in 
1908, the second in 1909, and the third in April, 1911 (five months ago). 
She has been insane for three months. There is roughening and pigmentation 
of the skin on the back of the hands and wrists, and extension around the 
wrists to the anterior or flexor surface. There is some scaling. Arterio- 
sclerosis complicates this case. 

The nervous symptoms are subjective complaints of headache, vertigo, 
weakness, precordial oppression, fullness of head, hot and cold flashes. The 
skin is dry. Hearing, sight, and smell are impaired. Temperature sense 



178 PELLAGRA. 

diminished. Muscular weakness. Deep reflexes are exaggerated, the plantar 
diminished, and the pupils react sluggishly to light and accommodation. The 
consensual reflex is absent. 

The mental symptoms are depression, and she is anxious, agitated, sus- 
picious, and somewhat confused at times. Delusions exist. There are hal- 
lucinations of sight and hearing. Orientation is impaired. Slight insight. 
Judgment impaired. Owing to lack of cooperation, retention, memory, etc., 
not tested satisfactorily. 

Termination, still under treatment. 

Unclassified Type. 

F. G., negro woman, aged 30, unmarried, agricultural laborer. The dura- 
tion of pellagra is unknown, and she has been insane for two weeks. The 
skin is dry and pigmented over the backs of the hands, the buccal mucosa is 
inflamed, tongue is red, fissured, and raw. Vaginitis is present, and prob- 
ably syphilis. 

The nervous symptoms are muscular weakness, deep and superficial reflexes 
exaggerated, sphincters not under control. 

The mental symptoms are indifference, and unusually destructive, filthy, 
noisy, and restless. Inaccessible to examination. 

Termination, death. 

ANALYSIS OF CASES. 

The following is an analysis of the sixty cases presenting evidence 
of pellagra on admission, and from which the preceding type cases 
are taken. These summaries are made by Dr. Green, and furnish 
much information hitherto unavailable in the study of the mind in 
pellagra. 

RACE AND SEX. 

White male 14 

White female 22 

Negro male 7 

Negro female 17 

60 
CIVIL CONDITION. 

Married 42 

Single 12 

Widowed 5 

Separated . 1 

60 

AGE. 

Average 38 

Youngest 18 

Oldest 69 



NERVOUS SYSTEM IN PELLAGRA. 179 



OCCUPATION. 

Farmer 10 

Farmer's wife 10 

Farmer's daughter 1 

Farm laborer 11 

Farm laborer's wife 1 

Domestic 8 

Housekeeper 3 

Minister 1 

Miller's wife 1 

Locomotive hostler 1 

Plumber's wife 1 

Salesman 1 

Salesman's wife 1 

Seamstress 1 

Mill operative 2 

Merchant's wife 2 

Stone cutter 1 

Laundress 2 

Machinist I 

None 1 

60 
DURATION OF PELLAGRA. 

Number of patients 30 

Average duration 8% months 

Shortest 1 month 

Longest 4 years 

DURATION OF INSANITY. 

Average duration 7 months, 1 week 

Number of patients 57 

COMPLICATIONS. 

Number of patients 31 

Pulmonary tuberculosis 10 

Syphilis 5 

Valvular heart disease 10 

Arteriosclerosis '. 6 

Chronic nephritis 1 

Enlarged thyroid 2 

Bronchitis, chronic 1 

Drug habit 1 



JO PELLAGRA. 



TERMINATION. 

Death 29 

Recovery 6 

Recovery from pellagra, mentally improved 3 

Removed unimproved 1 

Remaining under treatment, November 1, 1911 . 21 

60 



Summary of Nervous Symptoms. 

SUBJECTIVE COMPLAINTS. 

Headache 23 

Vertigo 20 

Weakness 8 

Pain 10 

Formication 6 

Numbness 7 

Nervousness 10 

Illness 6 

Indigestion 3 

Precordial distress 6 

IMPAIRMENT OF SPECIAL SENSES. 

Vision 3 

Hearing 8 

Smell 9 

Taste 2 

DISTURBANCE OF SENSATION. 

Hypesthesia 3 

Hyperesthesia 2 

Anesthesia 1 

Temperature sense ( impaired) G 

Stereognostic sense (impaired) 1 

MUSCULAR CONDITION. 

Weakness 42 

Rigidity G 

Twitching 9 

Contracture 1 

Incoordination 12 



NERVOUS SYSTEM IN PELLAGRA. 181 



REFLEXES. 

Deep. 

Exaggerated 42 

Diminished 7 

Absent 2 

Tremor 45 

Ankle clonus 7 

Convulsions 1 

Sphincter weakness 15 

Tenderness of muscle and nerve trunks 6 

Ehomberg's sign 9 

Babinski's sign 2 both sides 5 

Babinski's sign, right side only 1 

Superficial. 

Exaggerated 5 

Diminished 3 

Absent 6 

Pupillary. 

Sluggish 

Consensual absent 1 

GAIT. 

Unsteady 17 

Spastic 1 

Hemiplegic 1 

SPEECH. 

Indistinct 2 

Sticking 10 

Slurring 14 

Drawling 3 

Thickened \ 

Disturbed 5 

Summary of Mental Symptoms. 

Depression 25 

Retardation 15 

Suicidal 13 

Exaltation q 

Irritability q 

Distractibility 3 

Flight of ideas 2 



182 PELLAGRA, 

Volubility . . . 5 

Boisterousness . 12 

Restlessness 17 

Excitement 8 

Violence 10 

Erotic 1 

Obscene 1 

Profane 1 

Confusion 22 

Apprehensiveness 26 

Destructiveness 7 

Suspiciousness 5 

Inaccessibility 5 

Fabrication 3 

Incoherence 6 

Apathy 11 

Resistive 9 

Negative 3 

Mute 7 

Seclusive 3 

Not spontaneous 7 

Irrelevance 4 

Contradictory statements 1 

Catalepsy 6 

Refusal of food 5 

Mannerisms 5 

Impulsive acts 1 

Change of personality 2 

Drowsy 2 

Filthy 9 

Mumbling 4 

DISORIENTATION. 

For place 2 

For time 8 

For time and person 3 

For time and place 4 

For time, place, and person 26 

MEMORY IMPAIRED. 

For recent events 3 

For remote events 1 

For recent and remote events 25 

More for recent than for remote events 4 

More for remote than for recent events 6 



NERVOUS SYSTEM IN PELLAGRA. 183 



RETENTION. 

Impaired 34 

Lost 11 

GRASP ON GENERAL INFORMATION AND SCHOOL KNOWLEDGE. 

Impaired 16 

Much impaired 18 

COUNTING. 

Impaired 17 

Lost 3 

CALCULATION. 

Impaired 25 

Lost 9 

ATTENTION. 

Much impaired 16 

INSIGHT. 

Impaired 20 

Absent 25 

JUDGMENT. 

Impaired 27 

Much impaired 25 

HALLUCINATIONS (NUMBER OF PATIENTS, 41). 

Visual 3 

Auditory 14 

Visual and auditory 24 

DELUSIONS. 

Expansive 3 

Depressive 18 

Persecutory 34 

Influence 4 

Not stated 3 

When it is remembered how great are the changes in the indi- 
vidual cortical cells as stated by Spiller, the mental failure in pella- 
gra is easy to understand. It would seem in pellagra, as in tabes, 
that the changes in the brain vary in different cases. 



184 



PELLAGRA. 



DURATION OP HOSPITAL RESIDENCE BEFORE EVIDENCE OF PELLAGRA 

WAS NOTED. 

The following is a list of cases of pellagra reported in the Georgia 
State Asylum from January 1, 1911, to November 1, 1911, which 
showed no evidence of the disease on admission. 

Under 2 weeks 5 

2 to 4 weeks 4 

4 to 6 weeks 5 

6 to 8 weeks 3 

2 to 3 months 7 

3 to 4 months 5 

4 to 6 months 10 

6 to 9 months 6 

9 to 12 months 3 

12 to 18 months 4 

18 months to 2 years 4 

2 to 4 years 10 

4 to 6 years 8 

6 to 10 years 8 

10 to 15 years 1 

Over 15 years G 



89 



CHAPTER VII. 

OTHER SYSTEMS AND CHANGES. 

CIRCULATORY SYSTEM. 

The effect of pellagra on the circulatory system includes chiefly 
changes in the blood, both in the corpuscular elements and the 
hemoglobin content; a tendency to an increase in the pulse rate; 
a tendency to a decrease in the blood pressure ; and, lastly, tissue 
changes in the heart itself. All these show great variation in dif- 
ferent cases and in the different stages in these cases, but in gen- 
eral an attack accentuates them, and in the milder cases they are 
less pronounced during the intermissions. The blood is a tissue, 
although a fluid tissue, and it decreases in volume proportionately 
to the loss of weight of the body as a whole as the disease progresses. 
There are not only changes in the blood as commonly understood 
in medicine, but there is progressively less blood, The ever-recur- 
ring diarrhea removes appreciable amounts of blood serum, and 
more and more is this evident in the latter stages. 

The principal change in the corpuscles is an increase in the 
percentage of the small lymphocytes, and this is usually accom- 
panied by a decrease in the normal percent of polynuclear cells. 
This increase in the small lymphocytes is the one characteristic 
of the blood in pellagra. I give below two counts, the first of a 
woman 55 years old in the intermission period, up and about her 
household duties; the second was made by Low, of London, for 
Sambon, of blood from a 14-year-old, brought from Italy to Lon- 
don by the latter, during the recession of an attack. One is an 
American adult pellagrin, and the other an Italian child pellagrin, 
both females. 

American. Italian. 

Hemoglobin , 80 95 

White cells 4,500 8,400 

Reds 4,184,000 4,850,000 

185 



186 



PELLAGRA. 



DIFFERENTIAL COUNT. 

American. 

Polynuclears 52.6 

Small lymphocytes 33. 

Large lymphocytes 13. 

Eosinophiles 2. 

Myelocytes .6 

Transitionals . . 0. 



Italian. 
56. 
37.6 

4. 

4. 

0. 

2. 



The American case had "some irregularity in shape and size 
of the reds, though the centers were fairly good." Three hundred 
white cells counted. Low's notes on the Italian case stated: "The 
shape and size of the red cells were good. In the differential 
count it will be noted that the small lymphocytes are relatively 
increased" — 500 cells counted. 

This relative increase in the lymphocytes was further borne out 
by fifteen differential counts in as many different cases, 500 
leucocytes counted in each case. The counts were made by Low 
from cases brought from Italy by Sambon. When this excess of 
lymphocytes was absent, there was usually something to account 
for it, "such as polymorphonuclear leukocytosis due to sepsis or 
relative increase of the eosinophiles, in all probability due to 
ankylostomiasis." (Low.) My own cases show this relative in- 
crease in the small lymphocytes, but with no change in the large 
mononuclears. 

Hyde reports 9 counts from the Peoria cases, with an average 
red count of 3,930,000, hemoglobin of 79.3 percent, color index 
of 1.01, leukocytes of 15,400, with an average differential count in 
the 9 cases as follows: polynuclears, 69.77 percent; small lympho- 
cytes, 18.02 percent; large lymphocytes, 11.72 per cent; eosinophiles, 
.33 percent; basophiles, .16 percent. Hyde calls attention to the 
interesting fact that eosinophiles were found in only 4 of the 9 
cases, and those only after counting several hundred leukocytes, 
and over a thousand leukocytes were counted in some cases without 
finding a single eosinophile. Lavinder, in South Carolina asylum 
cases, made 24 blood counts, with an average hemoglobin of 69 
percent ; leukocytes, 9,048 ; reds, 4,473,260. He made differential 
counts in several of these cases, with a relative increase in the 
lymphocytes and an absence of eosinophilia in the uncomplicated 
cases. Egan made 26 red counts in Illinois, with an average of 
4,200,000 ; color index rather low, 1 or 0.9 ; occasionally microcytes 



OTHER SYSTEMS AND CHANGES. 



187 



and rarely megalocytes ; and several cases with an increased 
leukocytosis running up to 48,000 and down to 10,000. Buhlig, 
basing his clinical experience on the relation between the leukocyte 




Fig. 58. — Pellagrin. A robust Irish woman. Dermatitis on hands, forearms, and el- 
bows. Lesions under breast, probably due to pressure and sweat. (Courtesy of 
Dr. C C. Bass.) 

count and the outcome of the case, found that pellagrins with a 
high count die early. 

The anemia in pellagra does not average as low as in hookworm 
infection. As a rule, it is not severe enough to produce a marked 
pallor, or the weakness, palpitation, and fever characteristic of 



188 PELLAGRA. 

the more severe types of secondary anemia. If the percentage of 
hemoglobin rnns as low as 75 or lower, one should suspect intes- 
tinal parasites, or some accompanying and anemic-producing in- 
fection. The anemia in pellagra is of a secondary type, after the 
manner of a chlorosis, with a qualitative change in the red cor- 
puscles rather than a marked decrease in their number. The lack 
of coloring matter is evident on examination of the mucous mem- 
branes, especially of the mouth, and between attacks is apparent 
on the edges of the tongue. Tucker found this anemia noticeable 
in 42 out of 49 cases. The average hemoglobin percent in pel- 
lagra is near 80, though higher than this in the early stages and 
mild cases, and lower at times in the advanced stage or in the 
severe cases. The cause of this secondary anemia is found in the 
circulating pellagrous toxin and the accompanying disturbance of 
the body nutrition. 

The tendency of pellagra is to increase the pulse rate. In all 
cases the pulse rate is increased during the attack, and, while in 
many cases it may return nearly to normal if the case be not too 
advanced, in by far the majority of cases it is permanently in- 
creased over its healthy normal. In a series of cases the following 
rates were noted : 

1. Male, first attack, condition good pulse, 104 

2. Female, advanced, in bed, cachectic pulse, 88 

3. Female, advanced, in bed, neurasthenic pulse, 96 

4. Male, first attack, in bed pulse, 100; standing, 110 

5. Female, first attack, standing pulse, 96 

6. Female, neurasthenic, sitting pulse, 90 

7. Female, after five annual attacks, sitting pulse, 112 

8. Female, first attack, rapidly progressive, sitting .... pulse, 90 

For these 8 cases, taken at random, the pulse averages 98. In 
the very chronic cases common in Italy the rate is not so high, and 
even in the times of intermission it may run as low as 60 to 75. 
I have noticed, too, in the asylum cases, with the mind gone and 
body left in comparatively good state of nutrition, the pulse may 
be slow and full. Those insane pellagrins approaching cachexia 
show an advanced rate, and in all cases the character and rate of 
the pulse is an important prognostic sign. The faster the pulse, 
the more serious the single attack, and the continual increased 
rapidity of the pulse after the recession of the attack is ominous 
of the grave. When the pulse passes 100, the patient is on the 



OTHER SYSTEMS AND CHANGES. 189 

threshold of the danger line, and with a continued increase it may 
be taken as a certain sign of increasing peril. As death approaches, 
the pulse mounts, and after passing 130 it may be taken for granted 
that dissolution is not far off in the majority of cases. 

As a rule, the pulse is regular, soft, and compressible, and, as 
the disease progresses, becomes of increasingly smaller volume. 
The emaciated wrist and strikingly rapid and regular pulse forms 
one of the clinical views of pellagra. "With the decrease in the 
total systemic blood volume, the pulse decreases in volume, and 
becomes so small in the later periods of the malady that Procopiu 
has well called it the "filiform pulse." It is of wire smallness, 
like a filiform bougie. 

With the foregoing conditions of blood volume, general weak- 
ness, and rapid pulse, one is not surprised at the low blood pres- 
sure characteristic of pellagra. There are exceptions to this, and 
one is found in the maniacal attacks in insane pellagrins, in which, 
as Antonini has pointed out, there is a marked rise in the blood 
pressure. Siler, for instance, using the Stanton instrument on 
insane pellagrins, found an average pressure of 146 millimeters. 
Drewry, on the other hand, in 21 cases found it to average 112 
millimeters. I have found it as low as 85 millimeters in several 
female pellagrins, and only once in a woman, and that between 
attacks, was it as high as 150 millimeters. The average in both 
sexes ranges around 115 millimeters. There exists here somewhat 
a similar relation between pulse rate and blood pressure that Hare 
has pointed out in pneumonia, except, where pneumonia is acute 
and its duration counted by days, pellagra is chronic and counted 
by years. As the pulse in pellagra rises, the blood pressure falls ; 
and the greater the pulse rise, the lower the pressure fall. With 
a pulse of 130 we would expect a pressure of less than 100, con- 
tinually decreasing toward death. The relation of pulse and pres- 
sure, therefore, forms an important prognostic sign. 

Sambon examined fresh and stained smears of blood of more 
than sixty typical cases of pellagra, but was "unable to find any 
parasite, either protozoan or metazoan, that might account for the 
disease." Low had the same experience, but further searched for 
spirochete and filarial, and always with negative results. The 
study of the bacteriology of the blood has yielded no results of 
importance. Tizzoni reported the discovery of an organism in the 
blood, but this has not been confirmed in any degree. Lavinder 



190 PELLAGRA. 

has investigated Tizzoni's method, used his technic, planted blood 
on different culture media, and injected it into different animals, 
and all with absolutely negative results. Hyde's commission also 
attempted blood cultures, with negative results in all cases. Bass 
reported 8 out of 12 cases positive to the Wasserman reaction. 
Howard Fox tested 30 cases by the method of Noguchi, and found 
2 cases with a reaction of moderate intensity, and in 5 cases the 
reaction was only weakly positive. In the light of present re- 
searches, pellagra is not a disease in which, even when the reac- 
tion occurs, the Wasserman reaction or Noguchi 's modification of 
it is at all strongly positive. 

The pellagrous poison has no selective action on the vessels. At 
times in old pellagrins the arteries are sclerosed, but this is an 
incident of age and other conditions, and is not produced by pel- 
lagra. The heart shows tissue changes that are more characteristic 
of the disease. The heart is usually atrophied and smaller than 
normal, more rarely hypertrophied, and occasionally it is dry and 
friable, the musculature breaking easily under pressure. The 
characteristic pigmentation of pellagra is present in the cardiac 
fibers, producing the brown atrophy or brown induration of the 
myocardial structure. Barden found these pigment granules 
grouped around the nuclei. Fatty degeneration occurs, but not 
nearly as commonly as the pigmentation. The interstitial fibrous 
tissue undergoes development and involves the muscle fibers, and 
a true myocarditis may occur. Pellagra, by increasing the pulse 
rate, overworks the heart, and a myocarditis is natural. Valvular 
lesions in pellagrins are not due to the disease, but are rather 
complications. 

LUNGS. 

Pellagra seems to have no direct action on the lungs. Tuber- 
culosis is the most frequent pulmonary complication, but there is 
no doubt that many of these cases of tuberculosis complicating 
pellagra are the result of the arousal of a latent tubercular in- 
fection from the lowered resistance of the tissues due to the pel- 
lagrous toxemia. Tuberculosis in pellagrins is more common in 
asylums and institutions where confinement indoors is the rule. 
It is far more rare among pellagrins living in the country dis- 
tricts at home. The rural occurrence of pellagra accounts to a 
degree for the rarity of pulmonary tuberculosis in pellagrins. 



OTHER SYSTEMS AND CHANGES. 191 

Strambio first called attention to the presence of hydrothorax 
at autopsy. This transudation of fluid into the pleural cavity 
probably occurs late in the disease, and in the days just before 
death, due to the cardiac exhaustion and the embarrassment of the 
pulmonary circulation. The fluid is clear and the pleural surfaces 
smooth. Edema and hyperemia of the lungs is a common con- 
dition at autopsy. The increased respiration just before death is 
related to the hydrothorax. Early in the disease respirations are 
normal, and they are increased to any degree only when fever 
accompanies the attack, or extreme nervousness is present. 

TEMPERATURE. 

The older Italian writers considered pellagra a disease without 
fever. The lack of a clinical thermometer had much to do with 
their error. Fever in pellagra occupies a secondary position 
among the symptoms of the disease. We do not lay such stress 
on the temperature here as we do on the temperature in typhoid 
for example, where fever is a primary symptom ; nor even as much 
stress as on the temperature in tuberculosis, where it is prognostic 
of the activity of the tubercular infection. The temperature in 
pellagra is more nearly related in importance to the temperature 
in syphilis as a symptom of the disease, from which we may in a 
measure derive an idea as to the gravity of the attack, and also 
some idea of immediate prognosis. In pellagra we do not diagnose 
the disease from the temperature, just as we do not diagnose 
syphilis from the temperature. 

An individual may have pellagra without any fever during the 
whole of the attack. Sandwith, from a study of 158 of the Egyp- 
tian cases, found only 1 of this number with fever, and that one 
a fatal case with a temperature of only 100°. This almost absolute 
absence of fever is not nearly so characteristic of the cases seen 
in America. Out of one series of 50 cases studied by Tucker, the 
temperature was normal in 21, elevated in 25, and below normal 
in 4. This presence of fever at some time during the progress 
of the disease is characteristic of the American cases. It is true, 
the mild cases have a low fever, rising usually not over 100°, but 
I find a temperature even in these is not uncommon, especially 
during the height of the stomatitis and diarrhea, and at intervals 
for two or three days as high as 101° or 102°. On the other hand, 



192 



PELLAGRA. 



it is to be remembered that a case may continue during the entire 
course without any rise in temperature; and, on the other hand, 
there may be not only no fever, but the temperature may be sub- 
normal, running as low as 96°, and rare cases have been reported 
with the temperature as low as 92°. 

Fever is more apt to be present during the attack and during 
the third stage of the disease. In the majority of cases a rise in 
the temperature means an increase in the gravity of the attack, 
and the higher the fever the more serious the condition of the 
pellagrin. A decrease in the temperature indicates an improve- 
ment in the condition of the patient and a recession of the attack. 
Fever is more apt to be present in the second stage than in the 
first, and in the third than in the second. The temperature may 
be not over 100° until a short time before death, and may con- 
tinue to rise in the last days and reach 105°, rarely 106°, and 
occasional higher temperatures have been reported. By far the 
greater majority of American cases terminating in death are febrile 
in the last days. The fever is irregular, though it usually shows 
an evening rise. This is by no means constant, and it may intermit 
irregularly. In the acute cases the fever is remittent in type, 
lower in the morning and higher in the evening. The pulse and 
temperature in pellagra are not closely related. The pellagrous 
toxin affects the pulse far more than it affects the temperature 
curve, and there is no disease in which the pulse rate and tem- 
perature curve are more independent of each other. The increased 
pulse rate is a primary effect, and the temperature more incidental. 
Weakness, emaciation, anemia, and loss of blood volume are factors 
that tend to produce the pellagrous temperature. Generally a 
high or continued temperature makes a bad prognosis. 



BONES. 

There are no special changes in the osseous system in the majority 
of cases. Lombroso found in a number of cases that the ribs were 
brittle and broke easily, and occasionally other bones seem more 
fragile than normal. On the other hand, cases are reported with 
fractures of the long bones, with the formation of the ordinary 
callus, and rapid healing and recovery. Strambio noted the 
sternum and ribs presented an unusually bright-red color at 
autopsy. He also found a softening in some bones somewhat 



OTHER SYSTEMS AND CHANGES. 193 

analogous to the changes wrought by osteomalacia, but this is 
probably a nutritional change due to the inability of the system 
to furnish food to the bones and the withdrawal of the earthy 
constituents. Lombroso thought the brittleness of some of the 
bones depended on the eccentric external atrophy of the hard bone 
and the hypertrophy and activity of the medullary substance. 
This process produces thinning of the outer portion of the bone, 
with strain due to pressure from within. In the medullary sub- 
stance occur at times cells containing red corpuscles and variously 
pigmented. Further studies are needed on the bones, and such 
studies would doubtless show that pellagra has no special selective 
action on the bones as it has on the cord, but rather affects them 
secondarily, due to the enormity of the nutritional disturbance 
suffered by the rest of the system. The bones are harder, being 
part mineral, and therefore suffer least. 

WEIGHT. 

Loss in weight is one of the most constant symptoms in pel- 
lagra. Omitting the dermatosis, there is probably no one symptom 
always present in every case of pellagra, but there is hardly a 
more frequent symptom than loss in weight. It is as valuable as 
it is constant, especially as it gives one an exact idea as to the 
upward or downward progress of the patient. The information 
from a pair of scales is worth much of lesser wisdom in a case 
of pellagra. There is no uncertainty here. If the pellagrin is 
improving, he is gaining weight; if he is not improving, he is 
losing weight. At the pellagrosario at Rovereto out of 383 pa- 
tients treated during the years 1905 to 1907 inclusive, 375 pel- 
lagrins gained an average of 12.8 pounds during their stay and 
treatment, and 8 pellagrins lost an average of 5.5 pounds. These 
figures include both adults and girls and boys. I investigated this 
point at the pellagrosario at Inzago, where only boys and girls are 
treated. Forty boys gained during their stay of a month to five 
months an average of 6.2 pounds ; the smallest gain was 2.2 pounds 
and the largest 14.7. Following an attack of a disease with so 
great a wasting power as pellagra, such a gain seems woefully in- 
sufficient. The gain would probably have been greater recovering 
from some disease other than pellagra. As compared with the 
American cases, the important fact is that these Italian cases are 
mild and that there is a gain in weight. On the contrary, these 



194 



PELLAGRA. 



boys averaged under size and under weight at best, and the ever 
present hookworm probably infected many of them. 

Sandwith believes there is always loss of flesh during the attack. 
My own experience agrees with this as to the American cases. 




Fig. 59. — An x-ray illustration of the left hand of a female pellagrin, aged 36 years. 
Note the rarification at the ends of the bones. 



OTHER SYSTEMS AND CHANGES. 



195 



Out of 156 cases, 19 left with weight the same as on entrance, 
101 gained an average of 5.4 pounds, which means that two-thirds 
of these cases improved under treatment. Thirty-six lost weight, 
and in a fatal case 19 pounds were lost before death. After an 




Fig. 60. — Same case as Fig. 59. An x-ray illustration of the right hand, with similar 

rarification at the ends of the bones. 



196 



PELLAGRA. 



attack boys and girls gain out of all proportion to adults. The 
milder an attack, the less the loss in weight. As a chronic case 
progresses, more and more weight is lost at each annual attack, 
and proportionately less regained. In the more severe attacks ac- 
companied by fever the loss in weight is very rapid. It is not 
rare for from 10 to 40 pounds to be lost in a month, and after 
an attack for a gain of an equal amount to take place in a slightly 




Fig. 61. 



-Same case as shown in Fig. 60. An x-ray illustration of the cervical region. 
The bones are practically normal. 



longer time. The weight is lost faster during the attack than it 
is regained after the attack. It is a sign of gravity if weight 
continues to be lost during the period of recession following an 
attack. If this continues, the patient is passing into the subchronic 
or cachectic form, and the outlook is bad. I had one striking ex- 
perience of this kind with a case in which 16 pounds were lost 
during the attack, and emaciation continued after the patient was 
apparently over the attack. Death occurred with a weight of 98 
pounds, and a total loss from the beginning of the disease of 42 






OTHER SYSTEMS AND CHANGES. 197 

pounds. Elrod's case gained 48 pounds in three months. Tucker 
found loss of weight in 52 out of 54 cases, and the other 2 were 
mild and showed no loss. Zeller reports a case with a loss of 80 
pounds, and Tucker one with a loss of 75 pounds. 

GENITO-URINARY SYSTEM. 

Urine. 

The three characteristics of pellagrous urine are (1) a decrease 
in the twenty-four-hour quantity, (2) a decrease in the acidity, and 
(3) a decrease in the specific gravity. These changes are not con- 
stant, and are not to be expected in each case ; indeed, the urine is 
frequently normal in all details. The more severe or the more 
advanced the case, the more do these characteristics tend to appear. 
The analysis of the urine of two female pellagrins gives a fair idea 
of its condition: 

1. 2. 

Quantity in 24 hours... 20 ounces (600 cc.) 35 ounces (1,050 cc.) 

Reaction Faintly acid Faintly acid 

Color Clear, amber Clear, amber 

Specific gravity 1.015 1.005 

Albumen None None 

Sugar None None 

Indican Present None 

Microscopical Great numbers epithelial No pus cells, a few blood 

and pus cells, mucus, cells and epithelial cells. 

triple phosphates, and 

amorphous urates. 

Harris reports two cases with a quantitive estimate of the urea 
and inorganic constituents. The first is a female, aged 46 years; 
urine, 690 cubic centimeters in twenty-four hours; acid reaction: 
specific gravity, 1.015 ; no sugar ; trace of albumen ; urea, 16.32 
grams; phosphates, 6.63 grams; chlorides, 11.48 grams; microscope 
shows a few pus cells, but no casts. The second case is a female, 
aged 54; urine, 1,375 cubic centimeters in twenty-four hours; acid, 
and with a specific gravity of 1.004; no albumen or sugar; urea, 
11.60 grams; phosphates, 2.75 grams; chlorides, 12.55 grams; mod- 
erate amount of indican and skatol; Ehrlich reaction moderate; 
microscope shows nothing unusual. 

All these facts in regard to the urine of pellagrins can best 



198 PELLAGRA. 

be shown by constructing a table of averages showing the average 
condition and amount of normal constituents in the urine of healthy 
individuals as compared with the urine of pellagrins. Practically 
every condition which influences the body influences the urine, 
and, therefore, the comparison between these tables is subject to 
the widest variation: 

Normal individuals. Pellagrins. 

Amount in 24 hours 50 ounces (1,500 cc.) 33 to 35 ounces (1,000 

cc.) 

Color Clear, yellow, or red Yellow 

Specific gravity 1.020 1.012 to 1.015 

Reaction Acid Faintly acid to alkaline 

Albumen None Earely present 

Sugar None None 

Indican None Very common 

Urea About 1 ounce (30 to 40 10 to 18 grams 

grams) 

Sodium ehlorid 185 grains (12 grams) 12 to 15 grams 

Phosphoric acid (phos- 
phates ) 2 to 6 grams 1 to 6 grams 

Sulphuric acid (sulphates) .2 grams 1 gram 

Oxalates 10 milligrams 26 grams 

Uric acid 0.2 to 1.4 grams 44 grams 

Microscopical No casts Hyaline and granular 

occasionally 

These figures on the urine in pellagra are chiefly from work 
done in the laboratory of Professor Antonini and reported in 
the record of the Fourth Italian Congress on Pellagra. From the 
Italian reports it appears that indican is more common in the 
urine of American pellagrins than in the Italian, but this is 
probably explained by the fact that the Americans are far greater 
meat eaters than the vegetable- and fruit-eating Italians. Occasion- 
ally in the winter the urine of pellagrins has a specific gravity over 
1.020, which, however, decreases again with the onset of the spring 
attack. In one of these cases in January the urine was 1.028, acid, 
with large amount of albumen. Alkaline urine has been consid- 
ered an evil omen, but this is not true. I have seen acute pel- 
lagra rapidly fatal, with acid urine throughout its whole course. 
Sandwith found only 3 alkaline urines out of 168 cases. Tucker 
reported 3 cases with a specific gravity respectively of 1.031, 1.032, 
and 1,040. Albuminuria is relatively rare, but it is more often 



OTHER SYSTEMS AND CHANGES. 199 

seen than a typical nephritis with casts. Painful urination is 
often present in advanced and senile cases. The pellagrous odor 
so characteristic of the feces in advanced cases is not noticed in 
the urine. Incontinence of urine may occur toward the last, and 
the secretion of urine is uninterrupted until death. In nephritis 
complicating pellagra the ordinary edema is present, but it is not 
so severe as in nephritis without pellagra. (Procopiu.) This is 
probably due to the emaciation and loss of flesh. Procopiu found 
the diazo reaction present in 16 and absent in 32 cases tested. 

The kidneys may show no change, but as a rule they are either 
atrophied, present fatty degeneration, or the tissue changes typical 
of the different forms of nephritis. They are nearly always 
smaller than normal. The fatty degeneration may be limited to 
the tubules. Evidence of the involvement of the glomeruli is rare. 
There is no change in the adrenals. Bravetta found congestion 
of the parenchyma of the kidney, increase in the connective tissue, 
with a diffuse pigmentation. 

Sexual Organs and Functions. 

The sexual function is dependent in a large degree on physical 
strength. Certain diseases — as, for instance, tuberculosis — may in 
some individuals increase the sexual appetite. Pellagra diminishes 
the physical force, lowers the reserve power, has no exciting in- 
fluence on the sexual system, and its tendency, therefore, is toward 
a diminution of the exercise of the sexual power. This influence 
is not so marked in the early stages, when the strength is greater, 
but, with the constant inroads of the disease, the generative powers 
diminish, but even in the early stages the sexual power may be 
completely lost. Male pellagrins rarely have night emissions, and 
matters of sex do not concern their minds. The testicles show no 
characteristic change. At times slight atrophy is present, but this 
is rather a part of the systemic emaciation. 

Pellagra influences the menstrual period. In Italy, as a rule, 
the menses in female pellagrins are regular, but this is not the 
case in America. Out of 28 cases in one series, only 1 menstruated 
regularly, and she was the mother of six children and 44 years 
old. The other 27 varied from amenorrhea for one to three months 
to absence of the menses for six to eight months. This is prob- 
ably best, as it conserves what strength there is in the already 
anemic and oligemic patient. On the other hand, metrorrhagia 



200 PELLAGRA. 

may occur lasting several days, ceasing, and then reappearing 
without warning. This metrorrhagia is not only exhausting, but 
it may be painful. Leucorrhea and painful urination occur. The 
vaginitis has been discussed in the chapter on the Skin (page 132). 
The breasts atrophy as a part of the process of the general loss 
of flesh. 

Abortions occur in about 20 percent of cases, although a pel- 
lagrous female may give birth to a healthy child. Such a con- 
finement is apt to be followed by complications, and especially 
by post-partum hemorrhage. A pregnancy may relight a latent 
pellagra, with a rapid onset of a serious attack. Pellagrins should 
not marry, and pregnancy should be avoided, as it but hastens 
death in the already disease-shadowed woman. Pellagra may re- 
main latent until after confinement, and then develop during the 
expected convalescence. 

Inflammatory conditions of the vagina, uterus, and diseased 
states of the ovaries and tubes are more frequent in pellagrins. 
Leucorrhea adds to the inflammation of the labige. Just as there 
often occurs in the alimentary tract a rectitis, colitis, and enteritis, 
so in the female genital tract, especially during the attack, there 
may be found a vulvo-vaginitis, erosion of the cervix, inflamed 
cervical canal, and an endometritis. On the other hand, there may 
be a simple vaginitis with leucorrhea. Ovarian neuralgia, ovarian 
cysts, uterine fibroma, and the various displacements of the uterus 
are found frequently in pellagrins, but they are rather to be con- 
sidered as complications, whereas the vaginitis, endometritis, and 
leucorrhea, with menstrual irregularities, are directly due to pel- 
lagra. 

Complaints, especially in women, are lodged against the sexual 
organs. The female pellagrin becomes conscious of her pelvis after 
the manner of a sexual neurasthenic. I have seen several cases 
operated on for a supposed gynecological condition when in reality 
the woman was pellagrous, and her genital complaint was what 
Eleanor Saunders well called an "incidental" in the course of the 
disease, and, as she well adds, "the majority of such patients should 
be treated not as having a primary organic pelvic disease, but as 
suffering from functional or symptomatic disorders." The gyne- 
cologist and the surgeon may be thrown off their guard by the 
genital complaints of pellagrins. A history of loss of flesh, 
emaciation, diarrhea, recurring vernal lassitude, ought to raise the 



OTHER SYSTEMS AND CHANGES. 201 

question of pellagra before operation for anything is decided upon. 
Operations on pellagrins do not offer encouragement, and only a 
most severe reason should permit surgical procedures. 

ORGANS OF SPECIAL SENSE. 
Eye. 

There is no condition of the eyes pathognomonic of or peculiar 
to pellagra. On the contrary, normal eyes in well-developed cases 
of pellagra are rare, but the chief reason for these abnormalities 
lies in the systemic asthenia, the lowered nerve power, and the 
effect of the circulating toxins of pellagra on the nervous system 
and the ocular apparatus. Eye weakness is present, and the 
ocular muscles and visual powers become fatigued rapidly, but 
all this is but a localized example of a systemic nerve and mus- 
cular debility. Sir William Gowers defines the eye as an outpost 
of the nervous system, and well says that it "presents the most 
delicate example in the body of the relation of nutrition to the 
nerves." The state of the eye depends on the nutritional state 
of the nerves which supply its various parts, and in pellagra this 
nutritional state is strikingly lowered. Therefore, the eye changes 
in pellagra, while technically interesting to the oculist, are part 
of the larger toxic and systemic process influencing the whole body. 

F. P. Calhoun, of Atlanta, in his investigations on the eye in 
hookworm disease, finds somewhat similar conditions as are present 
in pellagra. He has seen 10 cases of cataracts depending on hook- 
worm infection, and in 1 of these which he showed me and in some 
others the hookworm infection was mild, and the cataract in his 
opinion was due to the effects of the toxins eliminated by the worms. 
As shown both by Fabricius and Procopiu, cataracts are of un- 
usual frequency among pellagrins, even pellagrous children de- 
veloping them in the form of milky cataracts. Welton, in his 
investigations in Peoria, refers to the fact that "early forming 
cataracts are frequently noted," and Tucker found cataracts in 
3 out of 45 cases; Whaley, in South Carolina, found cataracts in 
5 and cloudy lens in 1 out of 35 pellagrins. This tendency to 
cataract formation both in hookworm disease and in pellagra is 
due to the metabolic degeneracy of the entire system, the altered 
and lowered nutrition of the lens, as determined by the persistence 
of the hookworm and the pellagra poisons. 



202 PELLAGRA. 

The severity of the eye symptoms runs parallel with the severity 
of the general manifestations of the disease, and the findings of 
marked eye changes add to the gravity of the prognosis in pel- 
lagra and indicate in a large percentage of cases an early fatal 
termination. (Welton.) Among the eye changes depending on 
the general weakness are diplopia, or double vision; hemeralopia, 
or night blindness ; photophobia, or fear of light ; mydriasis, either 
unilateral or bilateral, but more often affecting the right eye when 
unilateral ; ptosis, lachrymation, and conjunctivitis. Other changes 
are shallowness of the anterior chamber, paralysis of one or more 
muscles, sluggish pupillary reflex, atrophy or redness of the papilla, 
sclerosis of the retinal vessels, dilatation of the retinal veins, with 
a grayish or yellow cloudiness of the retina. Whaley found a 
dilatation of the retinal veins very common, and Calhoun has no- 
ticed the same condition in hookworm disease. Ulcers of the cornea, 
retinitis, choroiditis, inflammation of the optic nerve, and a com- 
bined retinochoroiditis occur, but are more rare than the first men- 
tioned changes. The studies on the eye thus far have been made 
on cases rather far advanced and on asylum cases, and in both 
the nerve changes are apt to be pronounced. A study of the eyes 
of the mild and recent cases and a comparison with the ocular 
studies in asylum cases would add to our knowledge of the effect 
of pellagra on the eye. 

Ears, Taste, Touch, Smell. 

Pellagra has very little effect on hearing, and in far the majority 
of pellagrins hearing is normal. Tucker found it diminished in 
5 out of 46 cases, and Green found it impaired in 8 out of 60 
insane pellagrins. In some cases, when the ability to hear appears 
slightly diminished, it will be found due to the condition of apathy 
and silence rather than to lack of ability to understand when 
spoken to. It is evident also that with a series of organic changes 
in the brain and cord, emaciation, and nerve exhaustion, the other 
special senses, like the hearing, would tend to be dulled and less 
acute than in the vividly healthy. 

Taste and smell are in the majority of cases normal, and, when 
affected, are slightly diminished. In mentally sound pellagrins I 
have been unable to find any marked change in either sense. In 
certain sections of Italy the persistent salty or briny taste is com- 
plained of, and I have found this in a negro female in Georgia. 



OTHER SYSTEMS AND CHANGES. 203 

Green found it impaired in 2 of his 60 cases, and Tucker thought it 
was diminished in 21 out of 46 and "coppery" in 1 case. Smell 
was lessened in 9 of Green's cases, and in 6 of Tucker's 44 cases. 

The disturbances of sensation in regard to itching, pruritus, 
formication, and burnings have been previously discussed in the 
chapter on the Skin (page 121). The special sensation of touch 
is not affected to the extent that it is in such diseases as hysteria 
and locomotor ataxia. With the esthesiometer the distance between 
the points is increased in a number of cases, but not to any marked 
degree. On touching objects, change in sensation is often noted — 
the pellagrin complains that the objects feel "far away," and 
seems unable to relate the sensation of the object in his mental 
processes. The sensation to temperature is more often impaired 
than the mere sense of touch. In about 10 percent of cases this 
sensation of heat is lowered, and at times in the lower extremities 
may be so impaired as to remind one of .the changes in syringo- 
myelia. Anesthesia to cold may prevail in localized areas and 
hyperesthesia to heat, and vice versa. The systemic sensibility to 
heat and cold varies, and, as a rule, excessive heat is avoided, but 
I remember one pellagrin who sat in front of the fire constantly 
and seemed always more comfortable in the presence of such heat. 



CHAPTER VIII. 

DIAGNOSIS AND PROGNOSIS. 

DIAGNOSIS. 

The fundamental element in the diagnosis is to remember that 
pellagra is a definite disease, an exact morbid process, and separated 
from other diseases by well-marked symptoms. The longer one 
studies pellagra, the clearer are its symptoms and the more sharply 
it is defined as an entity. A diagnosis is made independently of 
any idea of its causation or of any theory regarding the etiology. 
In the present state of our knowledge, etiology and diagnosis are 
not to be considered together. If one attempts to relate his 
diagnosis to any pet theory he may have formed as to etiology, he 
is apt to find his theory influencing his diagnosis, and especially 
in the more difficult cases. The diagnosis depends on the symptoms 
presented and not on any theory as to cause. 

The diagnosis is made by the observation of the external clinical 
symptoms, the history, and the present condition of the patient, 
and it does not depend on laboratory findings to an important de- 
gree. It involves exact clinical observation, and in the present 
state of our knowledge the miscroscope is of little avail. It is true, 
in very obscure cases the increase in the lymphocytes in the blood 
may afford slight evidence, but one is not justified in making a 
diagnosis of pellagra on either the changes in the blood or the 
urine. In pulmonary tuberculosis the presence of the tubercle 
bacillus in the sputum clinches the diagnosis, in diphtheria the 
finding of the bacillus of Klebs-Loffler in the culture does the same, 
but in pellagra thus far there is no bacterium that aids in diagnosis, 
much less permits a positive diagnosis. The dermatosis clinches 
the diagnosis of a suspected pellagra just as the finding of the 
malarial parasite in the blood confirms a suspicion of malaria. 
Observation with the naked eye is of service. 

If in the future the history of pellagra in America' is what it 
has been in Italy, Egypt, and Roumania, the type will become 

204 



DIAGNOSIS AND FROGNOSIS. 205 

less acute and less severe, the course more chronic, and the damage 
wrought by the single attack far less because it will be more mild 
in character. It will probably increase among children, and in 
them the dermatosis be so temporary and slight as to resemble more 
the ordinary sunburn than a decisive diagnostic element in a very 
chronic disease. The acute and grave cases, rapidly progressive, 
are easier of diagnosis than the more chronic and mild forms. In 
these milder cases associated infections are present, and, as has 
been stated, the symptoms of pellagra may interlock with the 
symptoms of hookworm, for example; and, while the latter are 
easy to determine, the superimposed pellagra, especially in the 
latent period, may be difficult, if not impossible. The symptoms 
of pellagra are thus obscured by its very complications. Outside 
the dermatosis, which occurs during the attacks, the diagnosis is 
based not on one symptom, but on a group of symptoms, on the 
syndrome as a whole, and, with a suspicion of any associated in- 
fection, it is well first to take into account what conditions and 
symptoms are due to the associated infection, and then one is in 
a surer position to consider the remaining symptoms. One diag- 
nosis at a time, in one suspected of pellagra and a complicating 
disease, is a good rule. Then the real essence of a diagnosis be- 
comes evident— that pellagra is a disease diagnosed not on one 
symptom, but on the association of a group of symptoms. The 
tongue may be inflamed, and, considered by itself, would constitute 
a glossitis; but an inflamed tongue, with a diarrhea, a peculiar 
bilaterally symmetrical dermatitis, followed by a rough skin, a 
cedar-wood colored pigment, becomes a pellagra, which has as one 
of its symptoms a glossitis. 

Another factor in diagnosis is the fact that pellagra is not 
always active. It hides itself in the grass as a snake in its times 
of latency, and then reappears with the fury of fire in its attack. 
The attack may be very mild and short, and then the period of 
latency and hiding is long. Diagnosis is possible in the period 
of latency as well as in the period of activity, and the resting time 
presents a group of pellagrous sjanptoms, together with the his- 
tory, which permit a diagnosis. One should be as familiar with 
the symptoms of the latent period or intermission as he is with 
the classic symptoms of an attack. 

The diagnosis varies with the time of the disease, the severity, 
and the number of attacks. It is evident that if there have been 



206 PELLAGRA. 

repeated attacks, with a persistent pigmentation on the hands, 
roughness on the elbows, emaciation, slowness of the mental 
processes, the diagnosis is very much more easy than if only one 
or two mild attacks have occurred, and between them the patient 
has appeared about as well as usual. Pellagra appears to the 
physician for diagnosis in four different ways, and the symptoms 
on which a diagnosis is made differ in each of the four ways. 
These four appearances are as follows: 

1. Pellagra suspected by symptoms presented during onset. 

2. Diagnosis by symptoms presented during an attack. 

3. Diagnosis by symptoms presented in the intermission between 
attacks. 

4. Diagnosis by symptoms presented in the type pellagra sine 
exanthemata, or pellagra without the eruption. 

1. Pellagra Suspected During Onset and Before the Dermatitis. 
— Next to accuracy in diagnosis is the necessity for an early diag- 
nosis. The sooner a positive diagnosis is made, the more quickly 
can treatment begin, and the better the chances for improvement. 
Pellagra may be so mild that the patient is not aware of any 
prodromal period, and during the first or second attacks no need 
for consultation with a physician is felt. He is a little weak or 
languid, but nothing more. On the other hand, even in the severe 
cases, a physician is not consulted until the attack is at its height 
or great weakness is present. The period of onset may last several 
weeks, and the question arises on what symptoms may the physician 
with reason suspect an oncoming pellagra. A positive diagnosis 
at this time is uncertain, and in far the majority of cases impos- 
sible; but suspicion in diagnosis is the mother of attention, and 
generates careful examination for confirming evidence. 

The period of onset may last from a few days to three months 
in extreme cases before the dermatitis appears. Diarrhea without 
apparent cause may appear, and the tongue may be red on the 
tip and margins. Uneasy sensation in the abdomen, rumblings 
in the intestines in one previously healthy, together with the diar- 
rhea, not a dysentery, are suspicious. Along with these, insomnia 
without external cause, exaggerated reflexes and especially knee 
jerks, loss of energy, a continued sense of lassitude, add evidence 
for a suspicion of pellagra. Loss of flesh in the last few days or 
weeks, lowered specific gravity of the urine, and an increase in the 
small lymphocytes of the blood are important diagnostic points. 



DIAGNOSIS AND PROGNOSIS. 207 

A decreased acidity or total absence of free hydrochloric acid in 
the gastric contents in connection with the increased reflexes, the 
decreased specific gravity of the urine, the fact that the patient 
lives in a rural environment, and that the season is the spring time 
or early summer, would involve the necessity for an examination 
of the hands, elbows, and skin of the entire body. The physician 
should see the patient every second or third day for the confirma- 
tion of his suspicion by the appearance of bilaterally symmetrical 
dermatosis, or the error of his suspicion by the failure of such a 
dermatosis to appear. The physician here is in the same attitude 
of waiting as when he has a case of suspected syphilis and waits, 
as the elder Gross of Philadelphia advised, for the appearance of 
the syphilitic eruption. If this case of suspected pellagra is in an 
endemic pellagrous locality, and several cases have already de- 
veloped in the neighborhood, it bears careful watching. 

2. Diagnosis During the Attack. — A diagnosis of pellagra is 
made with ample evidence when the dermatosis appears. The 
appearance, localization, and development have been described in the 
chapter on the Skin (page 121). To summarize for purpose of 
diagnosis, it appears as the first symptom of pellagra in many cases, 
but in most cases follows digestive and nervous disturbances; it is 
bilaterally symmetrical, appearing always on the back of the hands, 
and it may extend to the elbows, face, neck, sternum, feet, and 
rarely to the trunk and thighs. Areas of roughness develop usu- 
ally on the elbows and more rarely on the knees, forehead, fore- 
arms, and legs; the dermatitis is reddish brown, like that of a 
dark-colored piece of red cedar wood. The dermatitis is followed 
by a persistent scaling, and it may occur several times in one 
season. After several attacks the back of the hands become perma- 
nently pigmented and rough, and the elbows become dry, rough, 
and divided into small rhomboidal areas. 

The skin condition is to be differentiated from four other skin 
lesions — sunburn, alcoholic dermatosis, eczema, and erythema multi- 
forme. In sunburn there is always a history of an unusual ex- 
posure to the sun, followed that night or the next day by the 
changes in the pigmentation of that skin area directly sun-exposed 
— as a rule, the back of the neck, the back of the hands, and the 
face. There are no constitutional symptoms, the patient knows 
the cause, the roughness on the elbows is lacking, the eruption heals 
quickly, and is not followed by a continual scaling and shedding 



208 PELLAGRA. 

of the skin. The alcoholic dermatosis appears in chronic alcoholics, 
with severe constitutional symptoms, the chief of which are an 
alcoholic neuritis, with pains in the lower extremities, wrists, and 
foot drop, a nephritis or uremia, and mental symptoms — as uncon- 
sciousness or delirium. The dermatosis — or ethylic erythema, as 
it is sometimes called — has an exfoliation of the epidermis on the 
back of the hands, a roughness of the elbows and knees, but there 
is no great pigmentation on the back of the hands. The alcoholic 
history is present ; the neuritis, the wrist drop, and the hands heal 
rapidly. 

The pellagrous dermatosis is to be distinguished from a dry, 
scaly eczema and an acute erythematous eczema. Itching is apt 
to be present in both of these, without a general constitutional 
disturbance, diarrhea, or sore mouth, and the skin lesions are not 
typically bilaterally symmetrical. In the erythematous form, too, 
slight irregularities or elevations of a pin-point character often 
appear on the reddened area. These are absent in pellagra. In 
erythema multiforme there is no scaling, the constitutional dis- 
turbance is slight or absent, and the spots have a bright-red areola. 
The eruption here is symmetrical, but the spots either in the papu- 
lar or bullous form are discrete and circumscribed, and cover a 
larger area than the ordinary pellagrous dermatitis. 

There may develop in chronic septicemia, alcoholism, or uremia 
a sore mouth, red tongue, raw and painful, and a stomatitis which 
involves the oral cavity. I have seen this condition once in a 
woman following an operation for appendicitis, with abscess and 
septicemia, and also in a case of acute uremia, and in a man with 
general alcoholic poisoning. Chronic septic conditions, alcoholism, 
or uremia cause mouth conditions closely simulating pellagra, but 
they are similar to pellagra only as regarding the mouth, and even 
here the tongue is more apt to be coated in the center, whereas 
in pellagra it is without a coat. The history of the case, anemia, 
acute nephritis, edema, alcoholism, septic foci and pus formation, 
absence of diarrhea and the dermatosis, serve to distinguish all 
these from pellagra. 

After the dermatosis is diagnosed as pellagrous, and the sore 
mouth and coatless tongue accompany it, whatever associated symp- 
toms of a pellagrous character exist alongside assist in the confirma- 
tion of the diagnosis. The diarrhea associated with the increased 
reflexes, the peculiar odor of the feces, the decreased gastric acidity, 



DIAGNOSIS AND PROGNOSIS. 209 

nausea, sensations of weight in the epigastrium, aversion to food 
or increased desire for food, gas in the intestines, associated with 
the dermatitis and the stomatitis, constitute a picture which per- 
mits of no doubt. The diarrhea may in the South cause one to 
think of sprue, especially as in sprue there is a sore mouth, but 
here the movements are whitish in color, lack the pellagrous odor, 
and the skin and nervous symptoms of pellagra are absent. The 
changes in the urine — as lessened acidity, specific gravity, and de- 
creased twenty-four-hour secretion — the increase of small lympho- 
cytes in the blood, the low grade secondary anemia, afford some 
further evidence. 

Among the general symptoms are the loss in weight, the spring 
or summer season, the rural environment, the retardation of the 
mental processes, the lack of inclination or ability to do work of 
ordinary character, the tendency to silence and the look on the 
dark side of life, and the desire for rest and inertia. The appear- 
ance is sometimes helpful. Just as one sometimes involuntarily 
thinks of hookworm disease when he is suddenly brought face to 
face with a patient severely infected, so the aged appearance, 
the stooped shoulders and bent gait, the thin angular face, the 
wrinkled and drawn forehead, the bronze or pinkish tint to the 
face, are all in turn characteristic of pellagra. The typical der- 
matosis, the tongue, mouth, diarrhea, and the increased reflexes, 
and nervous and mental symptoms, associated in the same patient 
at the same time, can give no trouble as to the diagnosis. The 
physician, to diagnose pellagra, must remember that the disease 
pellagra exists. Then the association of its plain symptoms makes 
the diagnosis during the attack very easy. 

3. The Diagnosis of Pellagra in the Intermission Between At- 
tacks. — In a few cases, preceded by very light attacks, the diagnosis 
at this time may be exceedingly difficult, but, as a rule, on close 
observation diagnosis is possible. The snake is in the grass, and, 
while we may not be able to see all of him at once, we can get 
glimpses of his head, his tail, or the middle of his body, clear 
enough to satisfy us that he is present. In the time of intermission 
what cutaneous, digestive, and nervous symptoms are present, and 
what general symptoms and points from history can be obtained, 
when associated together constitute a syndrome — peculiar to the 
latent time. 

What skin symptoms are present between attacks? The three 



210 



PELLAGRA. 



present in the majority of cases are the unusually pink fingers, the 
increase in the wrinkles over the first phalangeal joints of the 
fingers, and the roughness on both elbows. In old cases pigmen- 
tation may be found on the back of the hands, and the skin is 




Fig. 62. — Pellagrin after recovery from attack. Note contraction of little and ring 
fingers of left hand, following the severe dermatitis with edema. (Case of Dr. J. O. 
Elrod, Forsyth, Ga.). 

wrinkled, dry, and has fine branny scales which can be seen when 
looked at closely. The extensor surface of the forearm is often 
more rough than normal, and the whole hand may be strangely long 
and thin. Walnut-stained spots or chloasmic spots may remain on 



DIAGNOSIS AND PROGNOSIS. 211 

the face or neck, the forehead may be slightly rough or wrinkled, 
and a pink, drawn face add the final touch to the peculiar pella- 
grous facies. 

The digestive disturbances are wanting at this time, or there 
may be a complaint that digestion is not as good as formerly, the 
bowels are relaxed, and every few days several loose movements 
may occur, whereas the patient was previously constipated. Rum- 
bling and gaseous distention in the intestines may continue. The 
tongue now is usually coated, though not heavily, and the margins 
appear very clean. At the tip a few red papillae may be seen — 
by themselves meaning nothing, but, in association, the remnant 
of the former coatless and inflamed tongue of the attack. 

What nervous and mental symptoms are present? The general 
condition of the nervous system is according to the number and 
severity of the former attacks. In the mild attacks no great change 
is noticed, and the mind acts with its accustomed vigor. Even 
here, however, the pellagrin is unable to maintain the expenditure 
of physical strength over long periods of time, nor is his energy 
initiative in character — it rather flows with necessity and the 
routine of the day. He does not object to rest. Occasionally, on 
close observation, the hands will be found with tremors after slight 
exertion, and the fingers may tremble when separated and the arm 
extended. In a more advanced case the knee jerks are exaggerated 
and often markedly so, tremors and weakness are marked, the legs 
are unduly unsteady, and the gait more uncertain. The face and 
eyes are not those of a mentally active person, the pupils are often 
dilated, speech, while not disturbed, is slow, and few words are 
spoken. The history of the case differs from that of paresis, the 
specific gravity of the urine is less, speech disturbance is absent, 
and at this time the reflexes, with but few exceptions, are markedly 
increased, and the syphilitic pupil of paresis is absent. The history 
of the case, circulatory changes, nephritis, neuritis, alcoholic deli- 
rium, separate chronic alcoholism from pellagra. 

In women living in rural districts complaining of unusual lassi- 
tude and weakness for one or several spring seasons, a chronic 
vaginitis, a leucorrhea, cervical erosions, digestive disturbances, 
exaggerated reflexes and emaciation, or even with the symptoms of 
involvement of the genital tract absent, no operation should be 
considered or advised until pellagra is considered and ruled out as 
a cause. The same statement applies to this class of patients suf- 



212 



PELLAGRA. 



fering with gastric and intestinal symptoms. Gall bladder opera- 
tions on pellagrins neither cure the pellagra nor lengthen the life 
of the pellagrin. 




Fig. 63. — Pellagra in time of intermission. Patient has typical walnut stain on tipper 
lip, and yellow spots on face. Condition after three spring attacks. 

4. Diagnosis of Pellagra Without the Eruption, or Pellagra 
Sine Exanthemata. — It is doubtful whether a patient can have 
pellagra for a long series of years without any skin symptoms what- 
soever. For example, the dermatitis may be absent and the der- 
motagra present, or the dermotagra present only for a few days 



DIAGNOSIS AND PROGNOSIS. 



213 



when the digestive and nervous disturbances reach their height. 
It is true that pellagrins have pellagra without the dermatitis, and 
suffer a typical spring attack or more than one such attack with 
the absence of the dermatitis or a marked roughness of the skin. 




Fig. 64. — Same case as shown in Fig. 63. Elbow slightly rough; hands appear normal, 
except on very close examination, when fine branny scales are seen. 

In these cases the diagnosis is, of course, more difficult than when 
the characteristic dermatosis is present, but a diagnosis can be 
made. 

First, other diseases — as chronic dyspepsia, gastritis, amebic 



214 PELLAGRA. 

dysentery, neurasthenia, chronic hysterical temperaments, diseases 
of the gall bladder and intestines — must be considered and ruled 
out. Then the environment of the patient, history of spring sick- 
ness, flurries of diarrhea, sore mouth and coatless tongue, disturb- 
ances of digestion and uneasy sensations in the abdomen, absence 
or marked decrease in the hydrochloric acid of the gastric secre- 
tion, will give evidence from the alimentary tract. Nervous and 
mental changes peculiar to pellagrins, and especially the exagger- 
ated knee jerks, dilated pupils, retardation of ideas, loss of memory, 
emotional disturbances, will give more evidence. Finally, the 
presence of the triple changes in the urine — a decrease in the 
twenty-four-hour amount, the specific gravity, and the acidity — 
with slight secondary anemia, increase in the small lymphocytes at 
the expense of the polynuclear cells, serve to confirm or to dismiss 
our tentative diagnosis. Loss of flesh without other apparent cause 
is characteristic in this class of cases. 

PROGNOSIS. 

The prognosis in pellagra depends on the type of the disease 
with which the patient is affected. In that class known as acute 
pellagra, characterized by fever, prostration, high pulse, continued 
diarrhea, the prognosis is, of course, bad. These cases frequently 
recover from one or more attacks, and even very occasionally have 
no recurrence of the disease, but, as a rule, the outlook is bad, and 
the early advent of death may be expected. In the subchronic 
convalescent form the prognosis is bright, the attacks are mild, 
improvement is rapid, and permanent recovery is to be expected. 
In the subchronic cachectic form the progress of the disease is 
rapid; emaciation, high pulse, nerve symptoms, a more or less 
chronic diarrhea, make the outlook bad, though, of course, here 
final dissolution is neither as rapid nor as certain as in the acute 
forms. In the chronic form the prognosis is fair, and can be called 
neither good nor bad. Even if the disease is not cured, the patient 
will probably live for several years, and there is a reasonable hope 
of marked improvement. 

The prognosis varies in different countries, and thus far it has 
certainly been more grave and the mortality higher in this coun- 
try than elsewhere. For the nine years from 1901 to 1909 out of 
636 insane pellagrins, asylum cases, there were according to War- 



DIAGNOSIS AND PROGNOSIS. 215 

nock's report 93 deaths, or a mortality of about 15 percent. Sand- 
with, treating pellagrins not insane, found out of 437 treated in 
the years 1895, 1896, and 1897 there were 17 deaths, or a general 
death rate of 4 percent. These represent asylum and hospital 
cases in Egypt. Lombroso, quoted by Lavinder, for the year 1883 
in Italy, out of 6,025 pellagrins treated in the civil hospitals, noted 
923 deaths; and in 1884 there were treated in these civil hospitals 
6,944 cases, with 780 deaths, or an average mortality for both years 
of nearly 13 percent. Wollenberg collected a total of 55,029 cases 
in Italy in the year 1905, with 2,359 deaths, or a total mortality 
of slightly more than 4 percent. The mortality in Egypt and 
Italy is about the same. Babes and Sion are even optimistic of 
the cases in Roumania, and especially of those outside the asylums. 
I found that Fritz, at Inzago in the province of Milan, and Pro- 
bitzer, at the pellagrosario at Rovereto in Austria, will go through 
a whole year without a death, and more than 90 percent of their 
cases show improvement. It is rather the exception for a death 
to occur in those who come to these pellagrosari to be treated, and 
the death rate in Italy is dependent on the aged pellagrins, the 
chronic cases who have suffered many years, and the advanced 
asylum cases. The progress of pellagra in America will probably 
give the same history as to mortality in the near future. 

Contrasting these figures and data with the prognosis and 
mortality so far in America, it is clearly evident that the disease 
in this country is of a far more severe nature, more rapidly 
progressive, and proportionately more fatal. Bass, of New Orleans, 
has already called attention to the fact that the disease is less 
severe and acute in type in Louisiana than formerly, and it was 
with difficulty recently that he was able to find a case with the 
ordinary manifestations severely marked, whereas in 1908 and 1909 
such cases were common. Bresadola, in Rovereto, showed me a 
woman in September, 1911 — the worst case he had. She was 
up, walking around, and he remarked, indicating how the gen- 
eral type of the cases has lessened in severity, that in 1909, two 
years previously, this woman was the mildest case in the hos- 
pital. Indeed, Merk studied the disease in Rovereto, and gathered 
here the pictures for his great "Atlas on the Skin in Pellagra,' ' 
and now all these severe cases have ceased to develop in the Tyrol. 
As before stated, the disease will probably show the same evolution 
here in America, with an ever-increasing mildness in the individual 



216 PELLAGRA. 

cases, a decreased mortality, more cases which present a permanent 
improvement, and an increase in the length of the cases and a de- 
crease in the severity of the single attack. 

The asylum cases in America have had a mortality of between 
40 and 60 percent, with an average of about 50 percent. It is true 
that in the beginning there were a few places, as in Alabama, which 
showed for one year a higher death rate, and even this average of 
50 percent will probably decrease each year. The cases outside 
the asylums and treated by physicians in general practice have a 
mortality of about 25 percent, though frequently in different com- 
munities the death rate will be lower, and I have found physicians 
treating 20 cases in a county with only 2 deaths in a year, or a rate 
of 10 percent. Probably for the year 1912 the rate will not be 
over 20 percent. In the next five years in the United States the 
number of cases of pellagra will probably continue to increase, and 
the death rate will probably continue to decrease. 

The question arises as to the prognosis in the individual case. 
This is grave if the patient has any complications or chronic disease 
which reduce the strength and resisting power. Here are included 
surgical operations, frequent pregnancies, hookworm disease, tuber- 
culosis, and syphilis. It is the opinion in Italy and France that 
alcoholism predisposes to pellagra, and it is borne out in America 
to a degree. It is certainly true that an alcoholic bears pellagra 
badly, and in him the disease is usually rapid and the prognosis 
very grave. In my experience it is equally grave in chronic 
cigarette smokers, in those confined indoors for long hours, and 
in those whose purse does not permit change of diet and variations 
in the articles of nourishment. The prognosis in children is even 
more favorable than in adults. 

The attack in pellagra is often deceptive. The patient may lose 
20 to 50 pounds, lapse into unconsciousness, develop fever, pulse 
of 120, and seem near death, and then gradually improve, and in 
three months regain the lost weight. The character of the erup- 
tion offers no evidence as to the type of the case or its outcome, 
except in those few cases with the dermatitis so severe as to produce 
vesicles — the "wet" form — the cases are severe and the prognosis 
bad from the beginning of the first attack. Fortunately such cases 
are rarely seen and are decreasing in number. If the pulse rises 
over 100 with the patient in bed, the attack is severe, and over 120 
the patient is in danger as a rule. The same statement applies to 



DIAGNOSIS AND PROGNOSIS. 217 

a temperature over 100°, though, one sees cases with fever as high 
as 103 u improve and live several years. Continued diarrhea, with 
rapid loss of flesh, prostration, symptoms of delirium, subsultus 
tendinum, abolition of reflexes, are precursors of death. Before 
death the abdomen may become distended from a paresis of the 
intestines, and cause much discomfort. Contractures of the 
muscles, changes in the gait, mental decay, spastic conditions, ankle 
clonus, Babinski reflexes, are signs of organic changes in the cord 
and brain, and these organic changes are not subject to treatment 
or marked improvement. Rapid loss of flesh, severe prostration, 
high temperature, and rapid pulse unite to put the patient on the 
danger line. 

The prognosis is most favorable in proportion to the promptness 
of the diagnosis, the mildness of the first attack, and the per- 
sistence of the treatment. The prognosis is far better in the stage 
of dyspepsia, or the first degree, less so in the stage of neurasthenia, 
and hopeless in the stage of cachexia. Any case will live long 
in proportion to the severity of the injury to the nervous system. 
Recovery from the dermatitis does not mean the cure of the pel- 
lagra. The dermatitis may heal and the patient grow worse. The 
pulse, temperature, weight, and diarrhea are far better signals to 
watch and to follow than any evanescent coloring and scaling of 
the skin. The dermatitis never kills. The one best prognostic sign 
from month to month is the weight. There can be no mistake in de- 
pending on this great mass symptom of the disease. If there is an 
attack this spring, will there be another next spring? Here the 
physician is helpless. He does not know. There may never be 
another attack, or it may recur each spring until death, or, except 
for a slight lassitude for several spring seasons, a second attack may 
be delayed for several years. Despair on the part of the physician 
is as bad as despair on the part of the patient. A vast hope, backed 
by persistent treatment, brightens the prognosis in every case. 



CSAPTEE IX. 

TREATMENT OF PELLAGRA. 

Pellagra does not mean death. Treatment is of avail. Treat- 
ment certainly will not cure every case, and death will claim many, 
but careful medicinal, hygienic, and dietetic measures will give 
marked improvement in a majority of cases and prolong life. The 
question then arises as to how the physician knows when a case 
is cured. From the foregoing pages it is evident that pellagra 
is a durable disease, recurring annually or at longer periods. Be- 
cause the pellagrin improves and the evidences of his disease depart 
is no proof that the pellagra has gone or is cured. Therefore, one 
can speak correctly of a cure in a given case only when two or more 
years have elapsed, during which time the patient has shown a 
constant improvement in health and strength, and there has been 
no attack or return of noticeable pellagrous symptoms. 

"When a pellagrin recovers from an attack, it is manifestly in- 
correct and unwise to speak of a cure. There has been a recovery 
from a single attack, an improvement in the condition of the pa- 
tient, but it is too early to even use the word cure. The physician 
saves himself embarrassment later if there should be a recurrence. 
It takes time to pronounce a pellagrin cured, and recovery and 
improvement are strong enough words to use. When the attack 
recedes and the symptoms depart, the patient can well be said "to 
be improving and he will recover from this attack. " He is not 
at this time to be referred to as " cured. " As a result of treat- 
ment, the word improvement meets both the present situation and, 
on the other hand, does not imply that the following autumn or 
the next spring there may not be a recurrence of the attack. If 
the improvement is excellent, if the patient gains flesh rapidly, 
if the diarrhea, weakness, and nervous symptoms recede and 
strength returns, the patient may be said "to show a marked or 
radical improvement. ' ' If the condition of the pellagrin is such 
that so great improvement is impossible, and yet, as a result of 
treatment, he actually is some better, he may be said "to show a 

218 



TREATMENT OF PELLAGRA. 219 

satisfactory improvement." If he shows failure to respond to 
treatment, or the case rapidly assumes the cachectic form, there is 
simply "no improvement." No physician is wise enough to 
prophesy death even in the very severe attacks. He is often sur- 
prised at the very marked improvement that follows in cases that 
seemed near death. Even in. the most aggravated cases in the third 
stage, cachectic and prostrated, with dissolution apparently at hand, 
the patient frequently lingers far longer than expected. 

The first step in the treatment of pellagra is to ascertain whether 
any other disease is present. As stated before, pellagra is disease 
enough for any patient to have at one time. Its draining and re- 
sistance-lowering powers increase the capacity of any associated 
infection or disease to do greater damage. Pellagra affords fight 
enough to test the strength of the patient and the skill of the physi- 
cian. Any other disease increases the danger and lessens the 
chance of improvement from treatment. Pellagra acts as an alarm 
clock to awaken a sleeping infection. The pellagrin should be 
examined for tuberculosis, intestinal parasites, and malaria, and 
syphilis is not to be forgotten. The feces should be examined for 
amebas and especially for hookworm ova, and occasionally other 
ova may be found. In the South a latent malaria or hookworm 
infection is chiefly to be expected an associated infection. The 
treatment for either of these, if present, should be instituted when 
possible as soon as discovered, and the treatment of pellagra con- 
tinued at the same time. The cure of one of these associated infec- 
tions is really a part of the treatment of pellagra, because the 
pellagrin is benefited. Increasing the resisting power of the pella- 
grin is the first step in the treatment of his disease. 

There is a distinction between the treatment of pellagra and the 
treatment of any of its symptoms. Both require treatment and 
are closely related, yet the treatment of the dermatitis is not a treat- 
ment of the disease. The disease is internal, tissue-seated, silent, 
unseen, and progressive. The symptoms are external, objective, 
seen or felt, and recessive. The symptoms come and go ; the disease 
may remain. The symptoms improve as they disappear ; the disease 
lessens its activities in proportion as its external manifestations 
disappear. The dropsy from insufficiency of the mitral valve may 
disappear, but the insufficiency remains. The swelling goes, but 
the leak continues. The dermatitis and diarrhea go, but the 
disease within continues. The treatment is therefore twofold in 



220 PELLAGRA. 

character — (1) the treatment of the disease, and (2) the treatment 
of the symptoms of the disease. 

The treatment of pellagra is devoted against the disease itself 
primarily, and considers its objective symptoms only secondarily. 
It consists of medicinal, dietetic, and hygienic measures. 

MEDICINAL TREATMENT. 

There is no drug which cures pellagra. It has no specific. There 
is one best drug, and that drug is arsenic. It will not cure every 
case. Many cases will not improve under its use. If they will 
improve at all from the use of any drug, they will improve by 
taking arsenic. If no improvement follows its use, then the disease 
itself, not its symptoms, will not be influenced by any drug. If 
one takes the physicians in any average county, they will be found 
to be using a variety of drugs, often as many as twenty different 
ones, each physician using different ones to a degree, and all di- 
rected against one morbid process. It is certain that if it takes 
twenty, or even ten, drugs to cure or improve a patient, not one 
of them is of very much service, and all of them together had better 
be omitted entirely. 

Arsenic can well be given in full doses, and pellagrins can tolerate 
larger amounts than in possibly any other disease, except in the 
anemias. The following are preparations of arsenic chiefly used: 

1. Liquor potassii arsenitis, Fowler's solution, in doses of 5 to 
25 drops in water two or three times daily. Norton, at Cleveland, 
Georgia, gave a pellagrin 30 drops three times daily without un- 
toward symptoms. The dose can be increased and decreased in 
the graduated way, and a watch kept for the signs of saturation, 
such as puffy lids, swollen face, peculiar breath, and abdominal 
griping. 

2. In addition to the use of Fowler's solution by mouth, it is 
well, in order to give the largest amount of arsenic with the least 
danger and inconvenience, to administer hypodermatically one of 
the newer preparations. Of these sodium cacodylate, soamin, or 
atoxyl are to be preferred. Cacodylate of soda is probably less 
toxic than the others, the contained arsenic is liberated into the 
body slowly, and the maximum amount of arsenic is given with 
the minimum of toxic action. It is furnished in liquid form in am-"" 
pules containing 1 cubic centimeter of the solution, with either % 



TREATMENT OF PELLAGRA. 221 

grain or 3 grains (0.05 or 0.195 grams) of the salt, though a dose of 
5 or 6 grains can be given at intervals of two to six days in many 
cases with perfect safety. 

3. Atoxyl is the trade name of sodium arsanilate, and contains 
about 26 percent of arsenic. It is a white powder, readily soluble 
in water, and is furnished either in tablets or in ampules. It is 
given in doses of 3 grains, though often a pellagrin can take 5-grain 
doses without untoward symptoms. It is given, like the cacodylate 
and soamin, in intramuscular injections and under strict antiseptic 
precautions. 

4. Soamin is the trade name of sodium arsanilate, and contains 
about 22 percent arsenic. It is furnished in tablets for hypodermic 
use, and is given in doses of from 1 to 5 grains (0.06 to .32 grams). 

There is probably not a great deal of difference in the thera- 
peutic value of these last three preparations. They are all given 
hypodermatically, either subcutaneously or directly into the muscles, 
preferably the latter. One objection raised against them is that 
they should be given over long periods of time, but this very fact 
is of safety to the pellagrin, because it keeps his system under the 
influence of maximum amounts of arsenic. A point in favor of 
the cacodylate of soda is that large doses of this can be given with 
perfect safety. Elrod, of Forsyth, Georgia, has treated many cases 
with this preparation, and given as much as 5 grains a day for 
five days in succession with no ill effects whatever. On the other 
hand, the patients showed marked improvement, with gain in 
weight and increased appetite. 

Always strict antiseptic precautions are to be used. Lowered 
resistance of the pellagrin permits an easy entrance to infection, 
and all the more care should therefore be taken. Probably the 
easiest and safest way is to use a sterile needle and sterilize the 
area of administration on the skin with alcohol. This is the ordi- 
nary method in the hospitals, and with these arsenical preparations 
I have never seen infections follow. 

The chief point in the treatment of pellagra with arsenic is to 
give as large doses as possible compatible with the safety of the 
patient. I have noticed in my own cases the large amount of 
Fowler's solution that they were able to take without any deleteri- 
ous effect. Since the cause of pellagra is uncertain, the exact na- 
ture of the action of arsenic in this disease is unknown. It is 
certain that it is the one drug which seems to have a direct antag- 



222 PELLAGRA. 

onistic action on the disease. As shown by J. C. Muir, in the Jour- 
nal of Pathology and Bacteriology (1901, page 439), arsenic causes 
a decided erythroblastic reaction in the marrow of the long bones, 
and a slighter, but distinct leukoblastic, reaction. Whatever its 
action on the toxins, bacteria, or protozoa which may act as the 
cause of the disease, it stimulates the blood-making tissues to their 
full power, and, by the administration of either the cacodylate, 
atoxyl, or soamin, large doses are permissible. Such doses are 
absorbed slowly, and within reason have no cumulative effect. 

I have followed the following method in the administration of 
arsenic to pellagrins, and I owe to Dr. J. 0. Elrod, of Forsyth, 
Georgia, the idea of the beneficial results that follow the continual 
use of large doses of the cacodylate. In order to give the largest 
amount of arsenic, it is given by mouth as Fowler's solution, begin- 
ning with 5 drops in water two or three times daily, and increasing 
1 drop daily until untoward effects begin. Some patients will con- 
tinue up to 20 or 25 drops at a dose, but, as a rule, they do not 
stand well over 15 drops three times a day. Fritz, at Inzago, gives 
it in these doses only twice daily, increasing gradually. 

Cacodylate of soda, or one of the other preparations, is then 
given by hypodermatic injection, somewhat after Elrod 's method. 
He gives 3 grains (0.20 grams) every three days for three or four 
doses, then every two days for three doses. This is then increased 
to 5-grain (0.32 grams) doses every two days until the chief symp- 
toms have lessened or disappeared and a gain in weight has begun. 
By this method the pellagrin gets Fowler's solution internally, the 
cacodylate directly into the muscles, and in many cases a noticeable 
improvement begins. Babcoek has used soamin and atoxyl ; Martin, 
of Hot Springs, prefers soamin, and Williamson, of Graham, Texas, 
following Martin's method, gives 3 grains of soamin hypodermat- 
ically every other day, or at longer intervals up to 100 grains (6.5 
grams). The eruption, stomatitis, and diarrhea may show improve- 
ment from the beginning. The appetite is increased and the 
patient begins to gain weight. After the recovery from the attack 
the administration of arsenic should be continued for an indefinite 
period, giving Fowler's solution from 5 to 15 drops once daily, and 
a hypodermic of cacodylate of soda, or one of the other prepara- 
tions, from 3 to 6 grains (0.19 to 0.58 grams). I have repeatedly 
given these weekly injections of the cacodylate in 6-grain (0.58 
grams) doses, and the patient not only had no ill effects, but pre- 



TREATMENT OF PELLAGRA. 223 

sented a continued improvement. Arsenic is not to be dropped 
when the attack recedes; it is to be continued from one to three 
months after all the symptoms have disappeared, just as a physi- 
cian may give mercury or potassium iodid after all the noticeable 
symptoms of syphilis have disappeared. The following spring, 
even before there are any evidences of a subsequent attack, the 
arsenic should be commenced and given for from two weeks to a 
month. 

King and Crowell, of Charlotte {Journal of the American 
Medical Association, November 18, 1911), have treated 19 cases 
with salvarsan. They administered this by the intravenous method, 
giving salvarsan in doses of 0.6 gram, and to children 0.2 and 
0.3 gram. In case 1 five doses were given, one dose every twenty 
days. The symptoms disappeared and weight was regained. All 
these 19 cases showed improvement, and their histories in the spring 
of 1912 will be watched with interest. Martin prefers salvarsan. 
In some cases, since salvarsan is certainly the most powerful of 
the arsenical preparations, improvement will follow its use, but the 
difficulty and danger in its administration, the special apparatus 
necessary, and the expense to the patient do not seem to indicate 
that it will ever come into such general use as the less dangerous 
and, so far as is known, equally efficient cacodylate, soamin, and 
atoxyl. J. E. Paullin, of Atlanta, used the salvarsan in 9 cases, 
but was disappointed in his results. 

After the attack has begun to recede, or even during the attack, 
if emaciation and prostration are severe, it is at times beneficial to 
give cod liver oil in full doses, and tonics, such as iron in its various 
forms, strychnin, and even quinin in malarial districts. In the 
anemia following a pellagrous attack these may with wisdom and 
for convenience be combined in one capsule with the following, 
subject to variation: 

II Blaud's mass 3 j (3.9 gin.) 

Quinin bisulphate gr. xxx ( 1.9 gm.) 

Powdered capsicum gr. iij (0.19 gm.) 

Strychnin sulphate gr. j (0.064 gm.) 

Misce et fiant capsulse XXX. 

Sig. : 1 t. i. d. 

Sandwith, in Egypt, attached some value to tabloids of fresh bone 
marrow. In America this is prepared in liquid form as the elixir of 
bone marrow. I have been accustomed to adding small amounts of 



224 PELLAGRA. 

dilute hydrochloric acid and tincture of nux vomica to this, and this 
prescription seems to do good in those emaciated cases in which .the 
diarrhea continued and dyspepsia and flatulence are troublesome. 

Many physicians, following out one of Lombroso's ideas, feel 
called upon to give the chlorides in some form on the idea that the 
system is deficient in them. In Italy common salt or sodium 
chlorid is a government monopoly, and in former days, when pov- 
erty was more prevalent in Italy than at the present time, the 
peasants did not use enough salt because they were simply too 
poor to buy it. As a matter of fact, salt is used more freely in 
this country than in Europe, and, so far as I have been able to 
discover, pellagrins in America receive as much salt as they need 
in their ordinary diet. Certainly, if they need more, it can best 
be given as common salt in the food and not in medicine. 

H. P. Cole and J. G. Winthrop, of Mobile, Ala., have transfused 
20 cases of pellagra, and conclude: "We may safely resort to 
transfusion in the severe type of, cases, steadily retrogressing 
under approved therapeutic procedures. We have noted no ad- 
vantage in the employment of a donor who has recovered from 
pellagra as compared with the donor who has never had pellagra. 
There is apparently no advantage in the use of a relative for a 
donor as compared with the use of a nonrelative. " They show as 
a result of these transfusions 60 percent of recoveries. It is, of 
course, too early to state whether these cases were permanently 
cured. Bennett and Scott, of Austin, Texas, surgeons to the Austin 
Sanitarium, have transfused 16 cases, with recovery in 13, or 73 
percent. The account of their cases appears in the Bulletin of the 
Texas State Board of Health for October, 1911. Dr. W. S. Gold- 
smith, of Atlanta, and I used this method in 3 cases. We noticed 
in each case temporary improvement. Two of the cases subse- 
quently died, 1 is still living, but still shows signs of the disease. 
Operation for transfusion does not require an anesthetic, and in the 
majority of cases is not followed by any shock to the recipient. 
The operation certainly will prolong life in a number of pellagrins, 
but I have not been convinced that it is either generally advisable 
as a routine method in advanced cases, or that it results in a perma- 
nent cure of the disease. When these patients reach the degree of 
prostration which necessitates transfusion, it is probable that the 
organic changes in the brain and cord have proceeded so far that 
permanent improvement is hardly to be expected. 



TREATMENT OF PELLAGRA. 225 



DIET. 



The dietetic management of pellagra concerns diet — first, during 
the attack, when the stomatitis, glossitis, dyspepsia, and diarrhea 
are present; and secondly, diet in the intermission. 

Diet During the Attack. — The pellagrin should be on as gen- 
erous and as nutritious a diet as is compatible with his powers of 
digestion and the condition of his alimentary tract. His strength 
is to be conserved, and his diet is to him both a food and a stimulant. 
When the attack is at its height, the mouth raw and sore, solid food 
can not be taken. Even acid liquids — as orange juice, orange and 
lemon albumen, and grape juice — give pain, and are to be avoided. 
At this time soups or broths of the ordinary kind, milk, strained, 
oatmeal, coffee, tea, malted milk, may be used. Sweet milk may 
produce indigestion, and it can be peptonized, thinned with water, 
or lime water added, in the judgment of the physician. This 
liquid diet should be given during the height of the attack every 
two to four hours and pressed as far as possible. Occasionally the 
pellagrin at this time may be nauseated, and for half a day or even 
a day or two be unable to take but little food, and then the mouth 
heals rapidly, the nausea lessens, and nourishment can be taken 
every two hours. It is a good rule to follow, as far as possible, 
the appetite, and, when the patient can and will take nourishment, 
to give it. Buttermilk and lactone are of service here, and in many 
cases are pleasant to the patient. As the attack recedes and the 
patient improves, a general diet may be given. 

Diet Between Attacks. — As convalescence begins, the liquid 
diet may be changed to a light diet, with the addition of mashed 
Irish potatoes, mashed sweet potatoes, boiled or scrambled eggs, 
butter, toast, scraped beef, rice with milk, and fruits. It is well 
at this time to give the three ordinary meals at breakfast, dinner, 
and supper, and nourishment at 10 :00 a. m., 3 :30 p. m., and bed- 
time. I have found in this way, by forcing the diet, improvement 
is more rapid and the patient takes even more food than he thinks 
possible. At these intermediate times, buttermilk, sweet milk, milk 
shakes, orange albumen, may well be given. At bedtime a glass 
of milk, preferably buttermilk, aids sleep and increases nutrition. 

With continued improvement, the change from the light diet to 
a general diet may be made, with a continuance, so far as possible, 
of the nourishment between meals and at bedtime. Added to 



226 PELLAGRA. 

the articles already mentioned are meats, as broiled steak, roast 
beef, chicken, and fish. Hog meat is to be avoided. The pella- 
grin has lost flesh during his attack, and consequently there is a 
demand on the part of his system for protein containing foods. 
In addition to the meat, eggs can be freely given and the lighter 
varieties of cheese. Rice, hominy, the more easily digested vege- 
tables — especially potatoes, English peas, Boston baked beans — are 
favorites at this time. There may be some difference of opinion 
as to the use of hominy, but I have never seen any ill effects follow 
its use. Butter and fats are to be given in large quantities, and, 
as a rule, will be found to be digested easily. The pellagrin in 
his tissues demands protein, carbohydrates, and fats, and his diet 
is to be as generous as his condition permits and as his digestion 
is good. 

The question naturally arises, in view of the corn theory of pel- 
lagra, as to whether articles of food which contain corn are to be 
permitted. At the Peoria State Hospital 56 patients subsisted 
for one year on a carefully selected noncorn diet, and 56 patients 
in another group were given an excessive corn diet for a similar 
period. At the end of twelve months there were no developments 
that were in the least conclusive. A few cases of pellagra developed 
in each group, but, on the whole, the corn-fed patients showed 
fewer cases than the patients on a corn-free diet (Zeller, Journal 
of American Medical Association, November 18, 1911, page 1689). 
More than one hundred articles of food are manufactured from 
corn, and it is a staple article of diet in two hemispheres. In the 
present unsettled state of the profession in regard to the cause of 
the disease, many physicians hesitate to permit the use of corn- 
containing foods. In some patients I have forbidden their use 
and in others I have permitted it, and I have failed to see any 
difference in the results. Syrup is made from corn, starch is made 
from corn, hominy is made from corn, bread is made from corn, 
batter cakes are made from corn, muffins are made from corn, and 
in the southern states at least the majority of pellagrins, as well 
as the majority of nonpellagrins, eat corn in one form or another. 
If the physician believes corn to be the cause of pellagra, he will 
forbid his cases to use its products as food. If he does not believe 
corn to be the cause of pellagra, he will permit his cases to use 
its products as food. It is a matter of preference and not a matter 
of results. 



TREATMENT OF PELLAGRA. 227 

HYGIENIC MEASURES. 

Because a patient has pellagra is no reason for putting him in 
bed. It has been a custom, in certain localities in the South to put 
the pellagrin in bed as a part of the routine treatment. I observed 
this matter very carefully in Italy, and the impression was forced 
on me that, as a rule, better results will be obtained if the pellagrin 
is kept out of bed as long as possible. He may lie down in the 
morning and again in the afternoon, but to stay in bed day in and 
day out, unless his case is already hopeless, increases his weakness 
and his depression. As one learned Italian physician remarked 
to me, "As long as we can keep the pellagra patients strong enough 
to stay up and out of bed, the better for them." Sandwith, in 
Egypt, gave his patients an airing twice a day. While it is neces- 
sary, on account of the diarrhea, the extreme weakness, or the 
cachexia in the advanced stages, and in the infective exhaustive 
types among the insane pellagrins, for them to be in bed, I am 
convinced that the less the other cases remain in bed the better 
for their physical strength, their appetite, their digestion, and 
their mental condition. Close, dark rooms are to be avoided. 
Ventilation, shade, fresh air, and reasonable exercise when possible 
are all desirable. 

The pellagrin should have a daily bath. Extremes of heat and 
cold are to be avoided. Tepid water, to which has been added 
common salt or a lump of crude alum, is both pleasant and in- 
vigorating. I find the alum bath as suggested by Boggs in typhoid 
fever {Journal of the American Medical Association, June 25, 
1910, page 2124) soothing to the skin, stimulating, and even better 
than the plain or salt baths. The crude lump alum may be pur- 
chased at any .drug store. A small lump the size of an egg should 
be dissolved in a little hot water and then added to the tub of tepid 
water, and the bath taken as usual. The hardening influence of 
the alum bath on the dermatitis is pleasant, the exfoliation of the 
skin is hastened, and the tenderness of the elbows, knees, hips, 
and shoulders lessened. 

Climate. — Strambio, quoted by Sambon, called attention to the 
improvement that sometimes follows when the pellagrin changes 
his place of residence. One such patient, afflicted with the chronic 
form of the disease, with recurrence of spring attacks and who 
previously lived in the country, was retained by Strambio as an 



228 PELLAGRA. 

orderly in the hospital, and for three or four years the spring at- 
tack failed to recur, though there were evidences that the pellagra 
still remained in the system. Bass, of New Orleans, has recently 
called attention to the improvement in a few of his own patients 
after he had sent them to Denver and to Tennessee, where the 
altitude was higher and the climate cooler. I had a similar ex- 
perience with two cases, both of whom went to the mountains. 
Hutchins, of Atlanta, noted a marked improvement in a case he 
sent from Georgia to New York state. One possible reason for 
the improvement of a pellagrin who comes from the country dis- 
tricts to the city is this change of climate, which, together with the 
change of food, seems temporarily at least to result in a gain of 
weight, increased appetite, and more cheerful outlook. "Whatever 
the cause of pellagra, whether the disease be infectious or toxic in 
nature, the change of residence certainly removes the patient from 
the danger of reinfection and lessens the danger of more poison. 
Pellagra disappears in the winter, and the change to a cooler 
climate would certainly seem advisable when practicable. Of 
course, this is possible only in a few cases, and may result in tem- 
porary benefit if such a change is possible just after the attack. 

TREATMENT OF SPECIAL SYMPTOMS. 

Dermatosis. — The dermatitis, as a rule, needs no special treat- 
ment. The patient, during the attack with the dermatitis in full 
bloom, should not be exposed directly to the sun, but should re- 
main in the shade. Neither should the patient at this time be 
exposed to artificial heat, as this aggravates the inflammation just 
as truly as does the sunlight. It is not necessary to bind the hands 
in bandages or cover them with cloths in order to keep out the 
light. The solution of iodin in oil in a 5-percent strength will 
hasten exfoliation when applied to the hands. As a rule, the oxid 
of zinc ointment is beneficial if the swelling of the skin is sufficient 
to cause tenderness, and as the dermatitis recedes this ointment 
prevents cracking and fissures, and hastens the shedding of the 
skin. If there is much itching, carbolic vaselin or equal parts of 
oxid of zinc ointment and lanolin, with a few drops of carbolic 
acid added, are soothing. If solutions are used instead of oint- 
ments, 1 :2,000 solution of cyanide of mercury once or twice daily, 
normal salt water, or weak alum water are all good. This alum 



TREATMENT OP PELLAGRA. 229 

water is prepared by putting a small lump of crude crystal alum 
into a bowl or pan of water. Its stringent effect relieves burning 
and itching temporarily in the hands and feet. I have found 
that in some patients this burning is relieved by cold applications 
or cold water, and in others warm water seems to do more good. 
The dermatitis with vesicles needs more careful treatment and atten- 
tion than the ordinary form. 

Diarrhea. — The diarrhea is to a degree dependent on the decrease 
in the hydrochloric acid, pepsin, and rennin of gastric juice. Dur- 
ing the height of the attack, however, when the diarrhea is apt to 
be worse, the stomatitis and the esophagitis make the mouth and 
esophagus so sensitive that the acid can be given only in small 
quantities, if at all. At this time a prescription containing tincture 
of nux vomica, bismuth, and elixir of lactated pepsin is frequently 
of service. This may be put in the form of an emulsion. Later 
another prescription containing dilute hydrochloric acid may be 
given when the condition of the mouth and throat permits. The 
administration of these artificial digestants not only tends to lessen 
the diarrhea, but also aids digestion, favors absorption, increases 
the stimulation, and promotes the metabolic activity, with a gain 
in weight. "When the diarrhea is very bad, and drains the patient 
to a serious degree, one should not hesitate to administer opium. 
Better a few hypodermics of morphin and rest than no rest and the 
loss of many pounds. Instead of morphin, an occasional dose of 
paregoric, codein, or even the deodorized tincture, may be given. 
On the days when the diarrhea is bad the patient should be quiet, 
but not necessarily remain in bed, and the diet should be either 
liquid or very light. 

Stomatitis. — The stomatitis and glossitis during the acme of the 
attack are not only very painful to the patient from sheer rawness 
in the mouth, but chewing, swallowing, and talking are actually 
interfered with. The gums are raw and tender, a tooth brush can 
not be used, and the mouth is not clean. A mouth wash here is 
of service, and the liquor antisepticus of the Pharmacopeia, or 
the liquor antisepticus alkalinus of the National Formulary, diluted 
with 1 to 3 parts of water, furnish mild and helpful alkaline mouth 
washes and gargles. If a physician has several pellagrins under 
treatment at one time, it is well to have one of the local druggists 
prepare a gallon or so of one of these preparations. Hydrogen 
dioxid, 1 part to 3 or 4 of water, or 1 ounce of chlorate of potash to 



230 PELLAGRA. 

1 pint of water, are of service. In lieu of the tooth brush, ab- 
sorbent cotton on tooth-picks, used with one of these solutions or 
with cold normal salt water, will tend to relieve the tenderness of 
the gums and remove particles of food from the teeth. At times 
the mouth is so tender that even such weak acids as orange juice, 
weak lemonade, or pineapple juice will give pain. "When the 
ulceration on the tip of the tongue and lips is marked, argyrol or 
nitrate of silver may be used, but, as a rule, the alkaline solution 
will be found sufficient. 

The increased flow of saliva occasionally calls for treatment. 
One grain of atropin to 1 ounce of water, each minim representing 
%80 grain of atropin, may be administered in doses of 1 to 5 
minims every two to four hours. An ice bag over the parotid 
gland, alternating from one side to the other, tends to relieve this 
condition. 

Nervous System. — The nervous system of a pellagrin, especially 
during the attack, is on edge. Narcotics and sedatives are to be 
avoided when possible, and, when given for insomnia or for an 
outbreak of mania or hysteria, should be administered in small 
doses. A cold sponge bath or an actual cold bath at this time is 
often of more service than a drug. The ordinary bromides, or 
5- to 10-grain doses of veronal, are usually sufficient. 

When insanity develops, the pellagrin should be put either in 
a private institution which cares for such patients or in a state 
asylum. No home is a fit place for an insane pellagrin. When 
they become insane, the highest form of real service both to them 
and to the immediate family is to place them where they can be 
really cared for and prevented from doing injury either to them- 
selves or to others. The average state institution in this country is 
presided over by physicians of high scientific attainment and 
ability. The asylums are clean, the food is good, all liberty com- 
patible with safety and order is granted. It may be a disgrace to 
go insane in some few cases, but it is no disgrace for an insane 
person to be cared for, and the place to be cared for is in an 
asylum. The physician, whenever the patient is insane and strong 
enough to travel, should advise removal to such an institution. 

Vertigo is not benefited to any degree by medicine. When it is 
severe, rest in bed, quiet, and slowness in walking, rising, or sitting 
is to be advised. 



CHAPTER X. 

CAUSE OF PELLAGRA. 

The cause of pellagra is unknown. The nature of the disease 
is in doubt. The pathology of the disease does not throw any light 
on its cause. It has been ranked alongside of many diseases. 
Prom the changes in the spinal cord it has been considered similar 
to syphilis and to such parasyphilitic diseases as locomotor ataxia 
and paresis. It has been compared to scurvy in that it was sup- 
posed to be due to errors in diet and poison in the food. It has 
been compared to leprosy, both on account of the involvement of 
the skin and on account of its power to produce cachexia and 
weakness. It has been assumed by many that pellagra is not a 
disease; that the syndrome of symptoms called pellagra does not 
constitute a distinct malady, but that these various symptoms be- 
long to other maladies, such as errors in the metabolism, diseases 
of the alimentary tract, primary degeneration of the spinal cord, 
the effects of bad heredity, and unknown conditions and processes. 
Pellagra is a disease whose cause is unknown. 

Two facts of a negative character are prominent in its history: 
(1) probably as many different causes have been assumed as there 
have been remedies given to cure it; (2) these causes, as numerous 
as they are, have been only assumed, and not one of them has been 
proved in a scientific manner. 

If we knew no more the cause of malaria than we do at present 
of the cause of pellagra, we certainly would be ignorant of the 
cause of the former. A theory is one thing and its proof is quite 
another thing. What is needed most in pellagra is the proof of a 
cause. It is true that we are not lacking in theories, but it is also 
true that the causes thus far advanced are only theories, and they 
have only been advanced. Each of them must forever remain in 
the domain of theory until one or all of them are shown to be 
incorrect, or until one of them, or a new theory, is shown to be a 

231 



232 PELLAGRA. 

true theory. It is not an opinion, but a proof, that gives us the 
cause of a disease. It may be possible that one of the many theories 
of pellagra may some day be proved. It may also be possible that 
not one of all the theories thus far advanced is correct, and a new 
true theory may come in, whose proof at one fell swoop will trans- 
form our present-day theories into memories. 

Among the causes that have been assigned for the disease is, first 
and foremost, Zea mais, maize, or Indian corn. It has been assumed 
to be due to bad nourishment, or poor food of whatever character. 
It has been assumed that any cereal, if given too long or damaged 
sufficiently, might cause the disease. It has been assumed that too 
little salt is a cause, and, again, that too little alcohol in the form 
of wine may cause it, and in Spain many physicians thought that 
too much alcoholism was the cause. The first great cause of pella- 
gra was considered to be the sun, then poverty, and the recurring 
answer has been that poverty and the sun are everywhere. As 
Procopiu well says, "the sun is not an appendix to any one coun- 
try." Along with malaria, its cause has been assigned to an un- 
known miasma, as unscientific as its nature is unknown. Billod 
believed that mania was the cause. Schelling believed that pellagra 
was more frequent in the presence of marshes and wet places. 

Against this theory of corn is the recent idea advanced by Sam- 
bon that it is an infectious disease caused by the presence of a 
parasite, either protozoan or bacterial, in the human body; and 
that this organism, whatever its character, is probably conveyed by 
an insect of some kind. In a broader way, these two theories may 
be expressed as follows: 

1. Pellagra is an intoxication. 

2. Pellagra is an infectious disease. 

The evidence and arguments for each of these theories will be 
given in detail. 

IS PELLAGRA AN INTOXICATION? 

For more than a hundred years, in an untold number of arti- 
cles and in books whose authors have devoted much study to the 
problem of pellagra, Zea mais or corn has been held to be in some 
way the cause of the disease. Two schools have arisen — one, repre- 
sented chiefly by the Italians, the French physicians, and the physi- 



CAUSE OF PELLAGRA. 233 

sians of Austria, believe that in some way pellagra is an intoxication 
caused by poisons contained in Indian corn, and those holding this 
belief are called Zeists; another group, represented chiefly by 
physicians in Spain, by Sambon and his followers, and by occa- 
sional physicians in the three countries above mentioned, do not 
believe corn to be the cause of the disease, and are therefore called 
anti-Zeists. Marzari, in 1810, stated the positive view that corn 
was the only cause of the disease, and on this proposition the dis- 
cussion and the difference of opinion has continued. Suffice it to 
say that after a hundred years of research, of study, and of ex- 
perience with the disease, the Zeists still differ among themselves as 
to just how corn does act as a cause, and, in the language of one of 
their number, ' ' with the accumulated evidence of a hundred years 
they still assume, but do not prove, that corn is in some way the 
cause." If corn is the cause, more concentrated evidence must be 
brought forward before the corn theory meets wider acceptance. 

The history of Indian corn is given fully in Bailey's Encyclopedia 
of Agriculture and in the Encyclopedia Britannica. It seems to 
have originated in South America, and to have been carried to 
Spain by the Spanish soon after the discovery of the American 
continent. There are seven varieties of corn commonly known: 

1. Zea mais tunicata, or pod corn. Each kernel is inclosed in a 
husk. Grown in Brazil. 

2. Zea mais everta, or pop corn. The grain has a large propor- 
tion of endosperm. Ear and grain both small. 

3. Zea mais indurata, or flint corn. Endosperm starchy and in- 
closed in a horny layer. Color of grain white, yellow, red, or 
mottled. Cultivated in Canada and northern United States. 

4. Zea mais indentata, dent or field corn. Starchy endosperm 
extending to summit of grain, inclosed in horny endosperm. The 
starchy matter is indented after drying and shrinking. This is 
the corn commonly grown and eaten in the United States. It is 
a low variety. 

5. Zea mais amylacea, or soft corn. White, red, or yellow, lacks 
a horny endosperm, with a uniform shrinkage of the grain. 
Formerly cultivated by the Indians in North and South America. 
Grown in Europe. 

6. Zea mais saccharata, or sweet corn. Garden corn, used as a 
vegetable and as canned sweet corn. 



234 



PELLAGRA. 



7. Zea mais, precocious and small. The ancient form in Peru, 
and found in the graves of the ancient Peruvians. 

ANALYSIS OF INDIAN CORN. 

The following is an analysis of Indian corn according to Bulletin 
298, "Food Value of Corn and Corn Products," by Charles D. 
Woods, D. S. C, United States Department of Agriculture : 

Table 1. — Composition of Different Portions of a Grain of Corn. 





Propor- 
tion in 
original 
grain. 

Percent. 


Water. 
Percent. 


In water-free material. 




Protein. 
Percent. 


Fat. 
Percent. 


Carbohydrates. 




Portion of corn 
kernel. 


Starch, 

sugar, 

etc. 

Percent. 


Crude 
fiber. 

Percent. 


Mineral 

matters. 

Percent. 


Whole kernel . . 

Skin 

Germ 


100.0 

5.6 

10.2 

84.2 


24.7 
15.3 
29.6 

24.7 


12.7 

6.6 

21.7 

12.2 


4.3 

1.6 

29.6 

1.5 


79.3 
74.1 
44.7 
85.0 


2.0 

16.4 

2.9 

.6 


1.7 
1.3 
1.1 


Endosperm .... 


.7 



Table 2. — Average 'Composition of Cereal Grains. 











Total carbohy- 
drates. 




Fuel 


Kind of cereal. 


Water. 


Protein. 


Fat. 


Starch, 

sugar, 

etc. 


Crude 
fiber. 


Mineral 
matters. 


value 

per 

pound. 




Percent. 


Percent. 


Percent. 


Percent. 


Percent. 


Percent. 


Percent. 


Indian corn . . . 


10.8 


10.0 


4.3 


71.7 


1.7 


1.5 


1,800 


Barley 


10.9 


11.0 


2.3 


69.5 


3.8 


2.5 


1,735 


Buckwheat .... 


12.6 


10.0 


2.2 


64.5 


8.7 


2.0 


1,600 


Kafir corn .... 


12.5 


10.9 


2.9 


70.5 


1,9 


1.3 


1,630 


Oats 


11.0 
12.0 


11.8 
8.0 


5.0 
. 2.0 


59.7 
76.0 


9.5 
1.0 


3.0 
1.0 


1,720 


Bice 


1,720 


Rye 


10.5 


12.2 


* 1.5 


71.8 


2.1 


1.9 


1,740 


Wheat 


10.6 


12.2 


1.7 


71.3 


2.4 


1.8 


1,750 



It will be noted from table 1 that nearly one-third of the germ is 
fat, and from table 2 that 4.3 percent of Indian corn is fat. 



CAUSE OF PELLAGRA. 



235 



Table 3. — Aveeage Composition of Corn Products and Wheat Flour. 





Water. 
Percent. 


Protein. 
Percent. 


Pat. 
Percent. 


Carbohydrates. 


Mineral 
matters. 

Percent. 


Fuel 


Kind of material. 


Starch, 

sugar, 

etc. 

Percent. 


Crude 
fiber. 

Percent. 


value 

per 

pound. 

Percent. 


Corn, whole grain, 


















10.8 


10.0 


4.3 


71.7 


1.7 


1.5 


1,795 


Corn with low pro- 
















tein content . . . 


10.5 


6.0 


3.8 


78.5 


78.5 


1.2 


1,685 


Corn with high 
















protein content 


10.5 


12.9 


4.4 


70.8 


70.8 


1.4 


1.695 


Corn, white 


11.4 


10.8 


5.0 


68.8 


2.5 


1.5 


1,690 


Corn, yellow .... 


11.9 


10.7 


4.8 


68.9 


2.2 


1.5 


1,690 


Sweet corn (ma- 
















tured ) 


8.8 


11.6 


8.1 


66.8 


2.8 


1.9 


1,750 




10.7 


11.2 


5.2 


69.6 


1.8 


1.5 


1,710 


Hominy^ fine .... 


11.0 


9.4 


.7 


78.2 


.4 


.3 


1,810 


Samp, coarse .... 


10.8 


8.3 


.5 


79.4 


.7 


.3 


1,770 


Corn meal (whole 
















grain ground ) , 


















12.0 


8.7 


4.7 


71.1 


2.2 


1.3 


1,850 


Corn meal (whole 
















grain ground), 
















bolted 


12.0 


8.9 


4.9 


72.0 


1.2 


1.0 


1,765 


Corn meal, granu- 
















lated 


12.5 


9.2 


1.9 


74.4 


1.0 


1.0 


1,770 


Corn flour — i. e., 
















finely ground and 
















bolted corn .... 


12.6 


7.1 


1.3 


77.5 


.9 


.6 


1,645 


Corn starch .... 








90.0 






1,675 


Liquid glucose ( for 












table use) . . . 


16.0 






83.5 






1,120 
4,040 
1,770 


Corn oil 






100.0 








Wheat flour .... 


11.1 


11.4 


1.3 


75.5 


.1 


.6 



Summing up the general composition with an average from all 
varieties, it may be stated that corn contains about 10 percent of 
water, 10 percent of protein, 4.5 percent of fat, and about 75 per- 
cent of carbohydrates and 1.5 percent of mineral matters. All of 
the five classes of foods are represented in corn — its fuel value is 
exceedingly high, and hence its wide use as food both for men and 
animals. 



236 



PELLAGRA. 



Table 4. — Composition of Cooked Corn Preparations, Corn Meal, 

and Wheat Bread. 











Carbohydrates. 




Fuel 

value 

per 

pound. 


Kind of material. 


Water. 


Protein. 


Pat. 


Starch, 

sugar, 

etc. 


Crude 
fiber. 


Mineral 
matters. 




Percent 


Percent. 


Percent. 


Percent. 


Percent. 


Percent. 


Percent, 


Hominy, boiled . . 


79.3 


2.2 


0.2 


17.8 


17.8 


0.5 


380 




52.8 


4.0 


.6 


40.0 


0.2 


2.4 


885 


Johnnycake 


29.4 


7.8 


2.2 


57.5 


.2 


2.9 


1,385 


Boston brown 
















bread 


43.9 


6.3 


2.1 


45.7 


.1 


1.9 


1,110 


Corn breakfast 
















foods, flaked, 
















partially cooked 
















at factory .... 


10.3 


9.6 


1.1 


77.9 


.4 


.7 


1,680 


Corn breakfast 
















foods, flaked and 
















parched ( ready 
















to eat) 


7.3 


10.1 


1.8 


77.2 


1 1.2 


2.4 


1,735 


Indian pudding . . 


60.7 


5.5 


4.8 


27.5 


27.5 


1.5 


815 


Cornstarch blanc- 
















mange (made 
















with cornstarch 
















and water) . . . 


87.3 


2.9 


.1 


9.5 




.2 


230 


Parched corn .... 


5.2 


11.5 


8.4 


72.3 


72.3 


2.6 


1,915 


Popped corn .... 


4.3 


10.7 


5.0 


77.3 


1.4 


1.3 


1,880 


Hulled corn 


74.1 


2.3 


.9 


22.2 


22.2 


.5 


490 


Granulated corn 


















12.5 


9.2 


1.9 


74.4 


1.0 


1.0 


1,655 


Wheat bread .... 


35.3 


9.2 


1.3 


52.6 


.5 


1.1 


1,205 



Figs. 65, 66, and 67 show a field of Italian corn and Figs. 68 and 
69 show Italian corn in the ear. Fig. 75 shows a field of American 
corn. The corn in Italy is planted in rows two feet apart. The 
ground is not prepared as well, nor is the crop cultivated as thor- 
oughly, as in America. On the Lombardian plains two crops are 
planted. The first, or chief, crop matures in September, and the 
second, or smaller, in October. The first crop in Italy averages 
about one ear to the stalk, and these ears are about two-thirds the 
length of the average American ear. The second crop would be 
called very poor corn in America, and the ear of this crop is about 
half the size of an ear of the first crop — about the size of what is 



CAUSE OF PELLAGRA. 



237 



usually called in America "nubbins." The Italian corn is prac- 
tically, without exception, yellow or red grains, while the Ameri- 
can and African corn is chiefly white grains. The Italians raise 
poor corn as compared with the American and African stan- 
dards. 

The corn in Italy is gathered in September and October, and is 
at once shucked and shelled. The whole family seat themselves 
around the corn pile and proceed to shell the grains. It is then 
spread out on a clean, well-swept dirt surface, and allowed to dry 
all day in the hot Italian sun. The seed corn is hung up in ears, 




Fig. 65. — Field of Italian corn, first crop; September, 1911. One ear on each stalk. 
Mulberry trees in background. Province of Milan, September, 1911. (Photograph 
by the author.) 

and the remainder, to be used and ground for food and for other 
purposes, is swept aside as shown in Fig. 71. The two reasons for 
the failure of the Italians to grow good corn are, first, their poor 
methods of cultivation; and, second, the close proximity of the 
mountains renders the nights too cool for the crop to reach the 
size and growth possible in America and Africa. 

Owing to the color of the corn grains, the corn meal of Italy is 
usually light-yellow in color. It is prepared in soft form (the 



238 



PELLAGRA. 



American corn meal mush) by mixing it with water and perhaps 
a little grease or fat, putting it in a pot, hung in the old-fashioned 
way from the chimney over the fire, and cooked for hours, stirred 
at intervals to prevent burning. It is then eaten somewhat after 
the order of the American hominy, or prepared in the form of a 
cake or pattie by frying or baking. This preparation is known in 
France as gaude, in Italy as polenta, and in Roumania as malaliga. 
Salt is used in mixing, or, before cooking, the dry meal is made up 
with salt water. The corn meal in Italy is often mixed with an 



! Iff J 


td li,* *4&- J'^ 


, .... 






.'» ' 


rr 






* % id 

■ 




I V 1 




» i ! 




wk ' itf ' 


• :t 








1 


■ 






i 










1 «, *■. 4*ar 


i^^^J^^w J -' . ~ JG iS^h 


• 


1 


4K.'. 


^THSSHB^B 


- ^■V- 




g04 







Fig. 66.- 



-Field of Italian corn, first crop; September, 1911. One ear on each stalk. 
Province of Milan. (Photograph by the author.) 



equal amount of wheat flour, and the whole baked in a cake a foot 
in diameter and cooked until it is hard and dry. This corn bread 
in Italy is known as pane giallo, or yellow bread. 

The different theories at present which consider corn to be the 
cause of the disease are, with one exception, built around the single 
proposition that corn spoils. It is useless to discuss in detail the 
numerous theories that have been advanced in the past hundred 
years in an attempt to show the change from good corn to spoiled 



CAUSE OF PELLAGRA. 



239 



corn, and the ingredients and poisons in spoiled corn which cause 
the disease. The following are the chief theories advanced: 

1. Good Corn Causes Pellagra. 

(a) Marzari in 1810 first advanced the theory that corn, and 
especially the poorer qualities, lacked sufficient albuminous material 




Eig. 67. — Field of Italian corn, second crop; September, 1911. One small ear or "nub- 
bin'' on eacb low stalk. Province of Milan. (Photograph by the author.) 

to be a good food, particularly a food on which people depended 
as largely as did the peasants of Italy at that time. Another 
phase of this same idea was advanced by the elder Strambio, who 
considered corn to lack a sufficient supply of nitrogen. 

(b) During the early part of the nineteenth century the more 
radical of the Zeists believed good corn to always contain a poison 
or a toxin of some kind, and that different people varied in their 
susceptibility to this poison. In this way was explained the fact 



240 



PELLAGRA. 



that, while every one in a community might eat corn, only those 
who were most susceptible to this poison developed pellagra. 

(c) Toward the close of the nineteenth century the idea was 
advanced by Neusser that good corn during digestion in the in- 
testines elaborated a poison which caused the disease. Later De 
Giaxa advanced the idea that the elaboration of this poison from 




Fig. 68. — Ear of Italian corn, first crop; red grains. (Photograph by the author.) 



good corn during digestion was due to the activity of the colon 
bacilli in the bowel. 

At the present time these three explanations of the corn theory 
are no longer held even by the more radical of the Zeists. Each 
phase of the proposition that good corn causes the disease is held 
to be unreasonable, and at variance with the universally accepted 
fact that good corn is one of the best and most nourishing articles 
of human diet. The seekers after an explanation as to just how 



CAUSE OF PELLAGRA. 



241 



corn does act or what it is in corn that acts as the cause turn to the 
proposition that 

2. Spoiled Corn is the Cause of Pellagra. 

This proposition is, in turn, explained in three different ways by 
three different schools of Zeists. 

(a) Various fungi found on spoiled corn are themselves poison- 
ous, and, when such corn is eaten, pellagra results. The pivotal 
point here is that the fungi poison the body, and are the cause of 
the disease and not the corn itself. Chief among these fungi which 
have been incriminated are penicillium glaucum, the common blue 
mold as seen on molded bread (Fig. 81) ; mucor racemosus and 




Fig. 69. 



-Ends of three ears of Italian corn; first crop; red grains. 

author.) 



(Photograph by the 



the species of aspergillus known as the green mold ; species of the 
saccharomycetes or yeast fungi ; oospora verticilloides ; and ustilago 
maydis, which causes the well-known corn smut. Spoiled corn is 
thus infected by these various fungi, and, when such corn is eaten, 
unknown poisons in the fungi cause pellagra. This idea is weak- 
ened by the fact that these different fungi can hardly all act as 
the cause of a disease, and yet each of them has its supporter among 
the research students of pellagra. 

(b) Various bacteria growing on spoiled corn are themselves 
poisonous, and, when such corn is eaten, pellagra results. The 
chief bacillus which has been incriminated both by Majocchi and 
Cuboni, and called by them the bacillus maidis, is now known to be 



242 



PELLAGRA. 



the common potato bacillus or bacillus solanacearum, the toxic 
effects of which are in no way similar to pellagra. Carrarioli, in 
1896, claimed to have found a bacillus in the blood, saliva, and 
stools of pellagrins, which he named the bacillus pellagras, and 
which he claimed to be the cause of the disease. He has had no 
support. Other bacteria have been put forward as the cause, but 
no evidence has been advanced sufficient to prove any one of them, 
(c) The fungi, chiefly the molds, cause corn to spoil, especially 
in the presence of prolonged dampness and darkness to which corn 




Fig. 70. — Method of drying shelled corn in Italy. Corn spread out on the ground in 
front of the thatched one-room structure, drying all day in the hot Italian sun. 
Building an example of one kind in which crop is stored. (Photograph by the author.) 

is subjected during shipment and in storage. The action of these 
fungi on the corn not only causes it to spoil, but permits the for- 
mation of poisons within the corn itself. These poisons which arise 
within the grain of spoiled corn are chemical in nature, and are 
the cause of pellagra. This represents to a large degree the idea 
of Lombroso, and this phase of the corn theory is called Lombroso 's 
theory, or the toxico-chemical or the toxico-infective theory of 
pellagra. 

Lombroso and others extracted from spoiled corn an oil of a 
yellowish or reddish color, known as the red oil of spoiled corn; 



CAUSE OF PELLAGRA. 



243 



and a solid substance yellow in color, alkaloidal in nature, called 
pellagrosine, or the toxic substance of spoiled corn; and lastly, a 
resinous mass known as the resin of spoiled corn. Lombroso made 
a mixture which contained all three of these substances and which 
he called the tincture of spoiled corn. Lombroso and his followers 
claim that when either damaged corn containing the three sub- 
stances or the tincture of spoiled corn is given to chickens, cats, 
dogs, and guinea pigs, the feathers and hair respectively fall out, 




Fig. 71. — Corn swept into another kind of building after drying in the sun. This is a 
better building than the one shown in Fig. 70. (Photograph by the author.) 

and there is a gradual development of cachexia, emaciation, diar- 
rhea, and death. These symptoms are believed by them to be the 
symptoms of pellagra and that the affection in animals so fed is 
the same entity as pellagra in man. 

At the present time the majority of Zeists lay more stress on the 
researches of Lombroso and on the idea that the bacteria and fungi 
cause poisons to be produced in the corn rather than the older view 
that fungi and bacteria are themselves poisonous. 

The following propositions are in support of the corn theory: 
1. Pellagra occurs in those countries where corn is cultivated and 



244 



PELLAGRA. 



eaten as food, as illustrated by Italy and the United States, where 
corn products are in universal use as food, in contrast with Eng- 
land, where corn is neither cultivated nor eaten to any degree, and 
pellagra does not exist. 

2. The disease followed the introduction of corn into Spain. In 
1840 corn was introduced into Egypt, and Pruner reported the first 




Fig. 72. — Cakes of yellow polenta. Italy, October, 1911. These cakes are made of yel- 
low corn. -meal and fried in grease. (Photograph, by the author.) 




Fig. 73. — American corn from Georgia, flint variety; keeps well. (Courtesy of Professor 
Fain, College of Agriculture, Athens, Ga.) 



case of pellagra in 1847 in that country. The prevalence of the 
idea that prophylactic measures taken against the use of poor and 
damaged corn will prevent pellagra and cause it to decrease in 
extent. 

3. Damaged corn given to chickens, dogs, and guinea pigs causes 
the feathers and hair respectively to fall out, a gradual develop- 
ment of cachexia, emaciation, diarrhea, and death. This disease 



CAUSE OF PELLAGRA. 



245 



in these animals is considered by the experimenters to be the same 
entity as pellagra in man. 

4. The changes in the spinal cord in pellagra are similar to those 
which take place in ergotism, a disease dne to a fungus growing on 
rye. 

5. Pellagra occurs only in people who eat corn or its products, 
and does not occur in individuals who abstain from corn or its 
products. 




Fig. 74. — Ears of American corn from Georgia, which do not keep well; spoil easily. 
(Courtesy of Professor Fain, College of Agriculture, Athens, Ga.) 




Fig. 75. 



-Field of American corn, Georgia ; two to four ears on a stalk. 
Professor Fain, College of Agriculture, Athens, Ga.) 



(Courtesy of 



6. The weight of opinion in Italy, Austria-Hungary, and in other 
regions where pellagra exists is in favor of the view that corn is 
the cause. 

7. Pellagra is not characterized by either high persistent or 
periodic fever, such as occur in syphilis, tuberculosis, and malaria, 
and is therefore more apt to be an intoxication than an infection. 

Objections to the Corn Theory. 

1. There is no agreement among the Zeists as to just what sub- 
stances or in just what way corn acts as a cause of the disease. 



246 



PELLAGRA. 



2. A poison is not apt to cause recurring seasonal attacks long 
after the patient has ceased to take it in his food. After a poison 
is removed, it does not remain in the system permanently, nor 
do its effects recur periodically. 

3. Corn does not explain why pellagra occurs among rural popu- 



















-hi 


y "^jfK^S 








feb - 




^u* »JK/ ^ .. ^jmM 


"'" : >«B 


$, <toR'~ 






; 


BjBffi v^ *~>>*4 


■5i^.*40MHl 




'-"'" <J? 


jgap- x ^sbi 




«fei - 


_"■ >| 




■■j 





Fig. 76. — One method of gathering and drying corn in America. (Courtesy of Professor 
Fain, College of Agriculture, Athens, Ga.) 




Fig. 77. — Rail pens without covers, sometimes used for storing unshucked corn in Amer- 
ica. Corn on the ear. (After Hartley, Farmers' Bulletin 313, United States De- 
partment of Agriculture.) 

lations and is practically absent from cities. "Why should the same 
corn cause pellagra in the country and not in the city? 

4. The numerous prophylactic measures — such as the inspection 
of corn, the drying of corn, the maturing of corn — have had no 
effect on lessening the prevalence and the severity of the disease, 
as illustrated by Spain, where practically no preventive measures 
have been taken and where the disease is nearing extinction due 
to unknown factors, and contrasted with Italy, where many pre- 
ventive measures have been taken and where the disease still exists 
over wide areas. 



CAUSE OP PELLAGRA. 



247 



5. The topographical relations of the disease to streams and the 
persistency of its endemic areas are not explained by the corn 
theory. 

6. The disease occurs in persons who do not eat corn or who 
have eaten it but rarely. The attacks of pellagra continue to recur 
in a pellagrin longer after he has ceased to eat corn. 




Fig. 78. — Cribs used for drying corn in the United States. Crib shown is 240 feet long, 
divided into bins 6x8 feet to facilitate drying of the corn. (After Hartley, Farm- 
ers' Bulletin 313, United States Department of Agriculture.) 

7. It is true that fungi cause such diseases as ringworm, acti- 
nomycosis, and the various mycetoma, but none of these resemble 
pellagra. This is evidence against the fungus theory of the disease. 



IS PELLAGRA AN INFECTIOUS DISEASE? 

A broad view of infection is given by Professor Kitchie in his 
article on the pathology of infection in Allbutt and Rolleston's 
' ' System of Medicine : ' ' 

The study of infection in its widest and most scientific sense is almost 
coterminous with, the study of the effect of any foreign living agent when it 
gains a foothold, and especially when it multiplies in the animal body. 
Another great truth has also emerged in modern times in the recognition 
of the fact that, notwithstanding the variety of clinical types produced by 
different agents, there is a great unity in the morbid processes set up. We 
must, therefore, in taking a broad view of the subject, be prepared to account 
for observed facts and to recognize common processes in such varied con- 
ditions as the following: 

1. The action of parasitic fungi and bacteria in such diseases as favus, 
septicemia, tuberculosis, diphtheria, enteric fever, etc. 

2. The action of parasitic protozoa in such disease as malaria, tsetse-fly 
disease, etc. 



248 



PELLAGRA. 



3. The action of what for the present are called "ultramicroscopic" living 
agents in such diseases as pleuropneumonia and foot-and-mouth disease in 
cattle, and probably yellow fever in man. 

4. The action of parasites of unknown character, though probably belong- 
ing to one or the other of the last three groups, which are in all likelihood 
associated with such disease as smallpox, scarlet fever, hydrophobia, measles, 
etc. 

5. It is a question whether certain phenomena associated with the presence 
of parasitic worms in the body ought not properly to be classed along with 
the phenomena of undoubted infections. 

These five propositions refer to the cause of that great group 
known in modern medicine as infectious diseases, and, if pellagra 
belongs to this group, its cause must come under one of these con- 




Fig. 79. — Diagrammatic section of a grain of corn, a, skin; b, germ; c, endosperm. 
(After Woods, Farmers' Bulletin 298, United States Department of Agriculture.) 

ditions of infection. The body of the pellagrin must, therefore, 
contain either living parasitic bacteria or fungi, which are the 
specific causes of pellagra and of no other disease ; or the pellagrin 
contain within his body parasitic protozoa or ultramicroscopic living 
agents or parasites of unknown character, causing diseases trans- 
missible by contact ; or, lastly, the body of the pellagrin must con- 
tain worms which act as specific cause of the disease. Now, it is 
necessary that the evidence which goes to show that pellagra is an 
infectious disease be presented in two ways : First, are the morbid 
processes carried on in the body of the pellagrin similar, in the 
widest sense, to the morbid processes characteristic of other known 



CAUSE OF PELLAGRA. 249 

infectious diseases, such as syphilis, malaria, sleeping sickness, 
hookworm disease, tuberculosis? This is the evidence from within 
the body, and may be called the pathological evidence of infection. 
Second, the evidence afforded from without the pellagrin, such as 
his relation to his environment, climate, temperature, home, stand- 
ing and running water, age, sex, occupation, and the history of 
the disease in one country for a long period of time. This may be 
called the relational or ecological evidence of infection. The dis- 
covery of the protozoan or bacterium which causes this disease is 
necessary before any absolute scientific proof can be given. 

(a) The Pathological Evidence That Pellagra is an Infectious 

Disease. 

1. There is a relative increase of the lymphocytes. Other proto- 
zoan diseases — as syphilis, kala azar — show a similar increase in 
these cells. Trypanosomiasis, or sleeping sickness, has a lymphatic 
infiltration of the brain with the mononuclear cells. 

2. Pellagra shows a marked increase in the lymphocytes of the 
cerebrospinal fluid. 

3. Pellagra shows at certain stages a marked leukocytosis, similar 
to the lukocytosis in malaria, which is a protozoan disease. 

4. Pellagra, syphilis, kala azar, malaria, and sleeping sickness 
are all alike benefited by arsenic. 

5. The nervous system is involved centrally as in syphilis, kala 
azar, and trypanosomiasis. These show an affinity for the spinal 
cord. Leprosy, an affinity for the peripheral nerves, and pellagra, 
like leprosy, has peripheral nerve formications, burning, numbness, 
pain. 

6. Pellagra, like malaria, shows a complete absence of eosino- 
philia. In pellagra as many as a thousand leukocytes may often 
be counted without the occurrence of a single eosinophile cell. 

7. Diarrhea is a characteristic of infective diseases, rather than 
a chronic intoxication, as illustrated by cholera and the choleraic 
or the algid form of malarial fever as contrasted with the constipa- 
tion of chronic alcoholism or beriberi. 

8. Like hookworm disease, pellagra produces eye changes and 
often causes the formation of cataracts. These cataracts are prob- 
ably due in hookworm disease to toxins elaborated by the worms 
and circulating in the blood and lymph for long periods. An in- 
fection may exist in pellagra with a similar elaboration of toxins. 



250 



PELLAGRA. 



(b) Ecological Evidence of Infection. 

1. Pellagra occurs in tropical and subtropical climates where 
infective diseases, and especially diseases caused by parasitic pro- 
tozoa and parasitic worms, are prevalent. Wherever pellagra 
occurs, malaria and hookworm disease are to be found, and nearly 
always amebic dysentery. 

2. Pellagra is not characteristic of climate in the northern sec- 
tions of the world, where the winter seasons are extremely long. 

3. Pellagra is a rural disease, and develops on farms and in 
homes whose environment is rural. It is not a city disease. 



>a 




Fig. 80. — Cellular structure of a grain of corn, a, skin; b, endosperm, consisting of 
(c) aleurone cells and (d) starch cells; e, membrane. 

4. Pellagra is more common in females than in males, and espe- 
cially is this true in America. Both eat the same food, and a food 
poison affects both sexes equally. There is a reason for the pre- 
dominance of female pellagrins, due in all probability to the fact 
that they are more exposed to the infecting agent. 

5. Children six months of age develop the disease in country dis- 
tricts. It seems more reasonable to believe the development of the 
chronic disease in an infant of this age to be due to an infection aris- 
ing from without than to poison in ordinary food given it infre- 
quently and in very small quantities. 

6. Pellagra bears a direct relation to the seasons in all countries 
where it exists. This is characteristic of infective protozoa and dis- 



CAUSE OF PELLAGRA. 



251 



eases like malaria, and is probably due to the more or less fixed 
life span of the parasite. Intoxications are not seasonal in their 
relations. 

7. Parasites, especially protozoa, are active in the spring, sum- 
mer, and autumn, and inactive in the winter. Pellagra is active 
in the spring, summer, and autumn, and latent in the winter. 

8. Infective diseases are widespread over the earth, as illustrated 
by such widespread diseases as tuberculosis, malaria, and syphilis. 
If pellagra is not an infectious disease, it is the only disease due 




Fig. 81. — Penicillium, a common mold found on corn. A, mycelium, with numerous 
branching sporophores bearing conidia ; B, apex of a sporophore enlarged, showing 
branching and chains of conidia. (Coulter, after Brefeld. ) 

to the ingestion of a poison formed in a grain that has so wide 
a distribution on the earth, is so chronic in its nature, and so per- 
sistent in its endemic relations. 

9. Infectious diseases are epidemic in character — as cholera, and 
endemic in character — as malaria. Pellagra is epidemic, as illus- 
trated by its recent invasion of America. It is endemic in char- 
acter, as illustrated by the fact that it exists in one mountain valley 
for a hundred years. 

Dr. Louis W. Sambon, an Italian physician, who lived formerly 
in the city of Milan, graduated in medicine at Naples and later 



252 



PELLAGRA. 



moved to London, where he is the present lecturer in the London 
School of Tropical Medicine, first advanced the theory that pella- 
gra is an insect-borne disease similar to sleeping sickness, malaria, 
and yellow fever. The evidence of this fact chiefly relates to the 
topographical relations of pellagra. 






Fig. 82. — Usailago maydis, a fungus that 
causes corn smut. A, staminate 
flowers of Indian corn, attacked by 
''smut''; B, mycelium, showing 
the beginning of spore formation; 
G, ripe spore (X600) ; D, germi- 
nating spore, developing a promyce- 
lium, with sporidia, E. (Campbell, 
after Bref eld.) 



Fig. 83. — The simulium fly and 
larva. (After Comstock.) 




Fig. 84.- — Wing of simulium fly, showing venation. 



1. Pellagra is a disease of place. It occurs in restricted areas in 
a country where it is endemic. Sambon found numerous illustra- 
tions of this in Italy, and Lavinder, with Sambon, was "frequently 
impressed with the statements of practitioners in pellagrous sections 
that all of their cases come from this or that restricted locality. ' ' 

The disease is found in an area, as a rule, at the foothills of 



CAUSE OF PELLAGRA. 253 

mountainous regions in areas traversed at frequent intervals with 
small streams. The vast majority of pellagrins in all the countries 
of the world where pellagra exists live in such areas. Now, in such 
areas in one of these mountain valleys many cases of the disease 
may originate, while no other cases may exist for miles around 
this valley. 

One of the most remarkable facts brought forward by Sambon 
as a result of his researches in Italy is that these endemic centers 
remain the same for a century. This is evidence in favor of the 
view that the disease is spread by an insect. He found that the 
present distribution of pellagra in the province of Bulluno is 
the same as that observed by Xecchinelli in 1818 and Odoardi in 
1776. Taking these three dates— 1776, 1818, and 1910— "the dis- 
ease affects the very same places along the valleys of the river 
Piade." 

2. Pellagra originates chiefly along streams and water courses. 
Sambon first pointed this out in Italy, and, following his example, 
I have found the same condition to exist in the southern states. 
The following table illustrates the relations of thirty-five pellagrins 
in Georgia to streams : 

Number of 
Number. Pellagrins. Residence. 

1 3 Swamp, three streams. 

2 3 Swamp. 

3 1 In 50 yards of stream. 

4 1 Location wet and swampy. 

5 2 In 14 mile of stream. 

6 1 Unknown. 

7 1 In i/4 mile of standing water. 

8 1 In % mile of branch. 

9 1 Between two streams. 

10 1 In 14 mile of pond and stream. 

11 1 In 300 yards of branch. 

12 1 On Chickamauga creek. 

13 1 In 220 yards of creek. 

14 1 In 300 yards of creek. 

15 1 In 14 mile of creek. 

16 1 On stream. 

17 1 On stream. 

18 1 Resided on pond 5 years. 

19 1 Between two springs and fresh branches. 

20 1 In 1 mile of stream. 

21 1 In 250 yards of stream. 



254 



PELLAGRA. 



Number of 
Number. Pellagrins. 



22 
23 
24 
25 
26 
27 
28 
29 
30 



Residence. 

In 200 yards of stream. 

12 years in 100 yards of stream. 

15 years in 100 yards of stream. 

In 1 mile of stream. 

In % mile of stream. 

In 30 yards of stream. 

On sea coast. 

In city. 

In 100 yards of stream. 




Fig. 85. — Legs of a chicken showing pellagrous symptoms produced by feeding maize 
spoiled by inoculation with a specific bacterium. (By Dr. C. C. Bass.) 



CAUSE OF PELLAGRA. 



255 




Fig. 



86. — Legs of another chicken manifesting similar symptoms to those of chicken in. 
Fig. 85. (By Dr. C. 0. Bass.) 



A single illustration from Sambon will suffice : 

It is a well-known fact among the peasants themselves that in pellagrous 
districts the disease is far more prevalent and severe in those who live quite 
close to a stream than in those who dwell at some distance from it on the 
neighboring heights. At Trestina (Citta di Castello), a place I visited in 
the company of Professor Centonze and Dr. Sediari, two peasants, Tommaso 
Paronni and Emidio Caracchini, told me that some years ago they used to 






256 



PELLAGRA. 



live by the Torrent Nestore, but that, owing to the severity of the disease, 
they had been obliged to abandon their houses near the stream and take 
refuge with their respective families on the Trestina hill. There are places 
on the Nestore, on the Minimella, and on a thousand other brooks and creeks 
where healthy newcomers invariably contract the disease. On several oc- 
casions I have seen families all the elder members of which were pellagrins, 
while the two or three youngest children were not, owing to the fact that the 
parents had removed from a pellagrous to a healthy locality before the birth 
of the latter. 




Fig. 87. — Bobbin Creek, near Athens, Ga., where the simuliuni larvae were first found in 
Georgia by Professor J. M. Reade. The larvaa are abundant on the rocks, where the 
water is swift. (Photograph by Professor J. M. Reade.) 

In July, 1911, Dr. L. B. Morse, of Hendersonville, N. C, became 
interested in the relation of pellagra to streams, and found in four 
cases in his community the disease originated while the patients 
were living near streams. Assistant Surgeon R. M. Green found 
the same conditions to exist in three counties in southwestern 
Kentucky, and regarding the 140 pellagrins which he found in these 
counties he writes as follows : 



CAUSE OF PELLAGRA. 257 

On account of the topography of the country, the most suitable locations 
for homes are along the streams, and consequently a large percentage of the 
inhabitants live along water courses. In every instance where I was able 
to visit the pellagrins at their homes I found them living within 500 or 600 
yards from a stream. A number of them were living in houses situated liter- 
ally on the banks of the streams. 

Fig. 88 shows an endemic pellagrous area in Dadeville, Ala. 
The stream in the center flows between the houses, those on the 
right being 200 yards away and situated on a hill. No cases de- 
veloped here. The houses to the left of the stream each contain 
pellagrins, which have developed while living in these houses. 
The family inhabiting house No. 2 moved away, and Mrs. A., who 
lived in the hilly portion of the town and was perfectly healthy, 
moved in. In a short while she developed the disease. These three 
homes are situated on a gentle slope just 75 yards away from the 
stream. One-half mile to the left a negro cabin was situated prac- 
tically on the stream. A negro woman and her daughter lived 
here, both developed the disease, and both died. It seems that the 
endemic area in this community was in the valleys trenched by 
these two streams, and the families that lived to the right on high 
ground were exempt. I know of no better evidence than is afforded 
by this simple illustration. I am indebted to Dr. J. Clarence 
Johnson for it and to his assistant, Dr. John Fitts, who made the 
sketch. 

J. O. Elrod, of Forsyth, Ga., showed me a similar endemic area 
in Monroe county. This endemic area w T as a valley in rolling mid- 
dle Georgia land, trenched by an ordinary small creek. Five cases 
of pellagra developed in this valley — one an old man, one a man 
of 40, two white women, and one negro woman. Fig. 89 shows 
the relation of a pellagrin to a stream in the village of Cornelia, 
Ga. In this case the patient had lived in a house for a great num- 
ber of years, and the disease originated here and here the patient 
died. While in Franklin, N. C, in the summer of 1910, I studied 
the premises and surroundings of a pellagra patient, a woman, 
who had recently died. The house bordered the road in front, and 
behind a branch of rapid mountain water ran within fifty feet of 
the back porch. On the right of the house was a perfect swamp, 
and the stream marked out a narrow mountain valley — exactly the 
same topographic conditions found in Italy by Sambon. 

K. H. Beall (Journal of the American Medical Association, 



258 



PELLAGRA. 




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260 PELLAGRA. 

November 18, 1911) is the only author I have found who disagrees 
with the relations of pellagra to streams. He studied 54 cases, and 
found that 4 lived in one-half mile of a stream; 9 lived from one- 
quarter to one-half mile; 41 lived at least one mile; 2 lived eight 
miles ; 4, ten miles ; 1, twelve miles ; 1, fifty miles, and 1 sixty miles 
from any overground collection of water — a general average of 
over four miles. 



INSECT CARRIER. 

Pellagra is not contagious, but spreads probably through the 
agency of its insect carrier as malaria or yellow fever are spread 
by insects. 

Alessandrini agrees with Sambon that pellagra in Italy is endemic 
along the borders of the streams, though he believes the cause to 
be a species of nematode worms of the genus filarida3. He ad- 
vanced this theory in 1910 in opposition to the corn theory, but it 
has neither been proved nor has it developed followers. From the 
foregoing it is evident that the same conditions in by far the larger 
number of cases prevail in the United States. Again, pellagra is 
rural and not urban. I was impressed with this at the hospital for 
the treatment of rickets and other deformities of the city of Milan. 
This very charitable institution sends out over the city every morn- 
ing and collects the deformed children of the poor, keeps them in 
the hospital all day for treatment and while their parents are 
working. I was told that in all their experience they had not found 
any of these children with pellagra, and yet their food is poor and 
certainly not any better than the food furnished the children in the 
rural districts in Egypt and Italy, where pellagra is common among 
children. It is evident that there is something in the country which 
is not in the city, and which is the cause of the disease. It is 
further evident that this something probably originates in or along 
streams, or standing water. Pellagra is not contagious, avoids the 
winter, develops in the spring and autumn, recurs and continues 
to redevelop at these same seasons. Pathological evidence affords 
reason for the belief that the disease is protozoan in origin. For 
all these reasons it is evident that pellagra is probably due to the 
agency of an insect of some kind. Sambon believes this insect to 
belong to the genus simulium. The following is a brief descrip- 
tion of this fly : 



CAUSE OF PELLAGRA. 261 

The simulium fly is one of the order diptera, or two-winged flies ; 
family simuliidge, with the one genus simulium, having many 
species. Of these Sambon found three species in Italy — simulium 
reptans, ornatum, and pubescens, chiefly the last. The two chief 
species in America are simulium venustum, or black fly, the great 
biter of the northern woods ; and simulium pecuarum, the southern 
buffalo gnat. This buffalo gnat causes the death of many mules 
and domestic animals. It is found along the tributaries of the 
Mississippi, through the state of Mississippi, possibly all of Arkan- 
sas, in Kansas, in Tennessee, Kentucky, and parts of Missouri, 
Illinois, and Indiana. Since 1850 this buffalo gnat has killed many 
thousand domestic animals. They appeared in the Mississippi valley 
as early as 1818, and in 1884 killed in Parrish, La., 300 head of 
stock in one week. They do not seem to appear every year in 
damaging numbers, but are always more numerous in time of flood. 
Sambon notes that in Italy the greatest number of pellagra cases 
occur in the flood and overflow years. 

Two crops of the insects emerge from the streams each year — 
one appearing from February to April, and the other from Septem- 
ber to December. The eggs are laid, when possible, in streams of 
rapid, shallow water, as in an ordinary branch or creek. Rock, 
leaves, and brush in the water are good places. They hatch in 
about eight days to a larva, passing in about four weeks into the 
pupa stage, and emerging in three weeks, after having spent the 
pupa stage in the bottom of the stream, as the mature two-winged 
fly or gnat. 

The Cambridge Natural History, vol. 6, page 477, defines the 
simulium or sand fly, or buffalo gnat, as "small obese flies with 
humped back, rather short legs and broad wings, with short, 
straight antennas, destitute of setse; proboscis not projecting; will 
probably prove to be nearly cosmopolitan. ' ' In Great Britain these 
flies do not increase to an extent sufficient to render them seriously 
injurious, but their bite is very annoying. Simulium columbaczense 
has caused great loss among the herds on the Danube. They prefer 
brisk and lively streams, as in rapids above the waterfalls, but 
have been found in sewage water. Further information about these 
flies can be found in the "Proceedings of the Boston Society of 
Natural History," Hagen, 1880, pages 305 to 307; American 
Entomologist, Osten Sacken from Verdat, vol. 2, page 229. De 
Geer's Memoirs (vol. 1, page 328) says they attack large, smooth 



262 



PELLAGRA. 



caterpillars, sucking blood, and Verdat has found them sucking 
honey dew from the aphidae. Osten Sacken (Berliner Entomolo- 
gische Zeitschrift, bd. 37, 1892) says the males love sunshine and 
swarm high in the air ; females remain at lower levels, and perhaps 
only females bite. F. M. Howlett, article on Indian Sand Flies, 
Congress of Medicine, Bombay, India, 1909. 

Dr. J. Cheston Bradley, assistant professor of entomology, 
Cornell University, was bitten by a simulium fly in the hotel at 
Clayton, Georgia, in the summer of 1911, and later, on a tramp up 
the mountains, found himself attacked again. He did not develop 
the disease, of course, but the point is that people in the pellagrous 
area are bitten by the simulium fly, and yet previous to 1911 this 
fly had never been reported from Georgia, and until Dr. Bradley 
was bitten it was not even known in that section that man was sub- 
ject to their attack. For the following reasons Sambon believes 
this insect to be the carrier of the disease: 

(a) Simulium, so far as we know, appears to affect the same 
topographical conditions as pellagra. 

(b) In its imago state it seems to present the same seasonal 
incidence. 

(c) It is found only in rural districts, and, as a rule, does not 
enter towns, villages, or houses. 

(d) It explains most admirably the peculiar limitation of the 
disease to agricultural laborers, a limitation which nothing else can 
explain in a satisfactory manner. 

(e) It has a wide geographical distribution, which seems to cover 
that of pellagra, although certainly exceeding it, in the same way 
that the distributional area of the anophelinae exceeds that of 
malaria, and the range of stegomyia calopus that of yellow fever. 

(f ) It is known to cause severe epizootics in Europe and America. 

(g) Other similarly minute blood-sucking diptera, such as 
phlebotomus papatassi and dilophus febrilis, are strongly suspected 
of being propagators of human diseases. 

The evidence so far in favor of the simulium is circumstantial 
evidence. So far as is known, where pellagra exists the simulium 
fly exists, but there are many species of this fly, and the question 
arises which one of these species is, or are all of them, the insect 
carrier. There are five species of the simulium in the Austrian 
Tyrol. There are many species in America, but the evidence thus 
far adduced is far stronger in favor of an insect as the carrier of 



CAUSE OF PELLAGRA. 263 

the disease than it is definite in favor of the simulium as the carrier. 
Sambon's argument and later evidence for an insect is very rea- 
sonable. Whether it is the simulium fly or not remains a problem. 
As pointed out by Chilton Thorington (Virginia Medical Semi- 
Monthly, July 21, 1911), the mosquito is to be borne in mind. It 
is not known whether a certain species of mosquito is common to 
all pellagrous areas, but certainly it should be determined whether 
the mosquito has any relation to the disease. The members of the 
genus ceratopogon of the family chirononiidas include the small 
midges commonly known as punkies. It should be determined 
whether these have any relation to the disease, as they, too, are 
blood-sucking and man-biting flies. Finally, Beall, formerly re- 
ferred to, has called attention to the fact that on account of the 
predominance of females in America it is reasonable to believe that 
they are more exposed to the disease. Of those males who developed 
pellagra in his series the majority of them were either under 20 
or over 50, and, like the women, spent most of their time at home. 
The predominance of females is greater in this country than in 
Italy or Roumania, and Beall believes this to be due to the fact 
that the insect w T hich causes the disease is one common to homes 
in the endemic districts and which bites during the day. If it were 
a night-biting insect, males and females would be equally attacked. 
This affords further evidence in favor of the necessity of investi- 
gating the mosquito as a probable cause, and the punkies. 

Objections to the Theory that Pellagra is an Infection. 

1. The failure to find in the blood, or in the tissues and body 
fluids, any parasites or specific bacteria. 

2. The failure to reproduce the disease when the blood of a 
pellagrin is injected into the body of a healthy person or into 
monkeys. 

Objections to the Theory that the Simulium is the Carrier of the 

Disease. 

1. The failure to find in the simulium any protozoa or specific 
bacteria. 

- 2. The inability so far to reproduce the disease when simulium 
flies are permitted to suck the blood from individuals suffering 



264 PELLAGRA. 

with pellagra and to then bite monkeys, as illustrated by the work 
done by the State Board of Health of Kansas. 

3. Lack of evidence to prove that blood-sucking flies other than 
those of the genus simuliidse may not be the carrier of the disease. 

At the present time further discussion of the cause of the dis- 
ease is to no purpose. If we knew the cause, it could probably 
be stated in a sentence — certainly in a page. Pellagra is either an 
infection or an intoxication — it can not be both. It can not be 
caused by the poisons of both corn and protozoa. Mizell, of At- 
lanta, has advanced the theory that cotton-seed oil and other oils 
are the cause, but so far no evidence — either chemical, physiolog- 
ical, or economic — has been advanced in favor of his idea. Bass, 
of New Orleans, like Lombroso, has fed chickens on spoiled corn 
and caused changes in the epidermis of the leg (Figs. 85, 86), even 
as Lombroso did before him, but that this is pellagra in the chicken 
is hardly probable. Would a continued diet of spoiled wheat, or 
spoiled oats, or spoiled buckwheat not cause a similar condition? 

Sambon's theory that pellagra is an infection has produced a 
profound impression. It is probable that the majority of physi- 
cians in Italy lean toward the corn theory. They have heard or 
been taught nothing else for a hundred years. It is probable that 
the majority of the physicians in the southern states lean away 
from the corn theory — certainly bear toward it the relation of the 
open mind. Many of them believe it to be an infectious disease, 
and I am inclined to this belief. The experiments now being 
carried on in the state of Kansas by Dr. S. J. Hunter (Journal 
of the American Medical Association, February 24, 1912), in which 
sand flies bite pellagrins and then are permitted to bite guinea 
pigs and monkeys, should bear some fruit. One of these monkeys 
so bitten became sick and developed fever. He was autopsied, and 
his nervous system is now being studied. Whether this experiment 
will result in anything is unknown, but it is at least along the 
right line. 

The advocates of corn have had a hundred years, and have not 
made out their case. Sambon's theory is but two years old, and is be- 
ing investigated. It behooves the Zeists to agree among themselves as 
to what it is in corn that causes the disease, and until this is done 
the burden of proof for the corn theory rests on them. It behooves 
Sambon and his followers to prove that pellagra is an infectious 



CAUSE OF PELLAGRA. 265 

disease, and to locate and name both the insect which acts as host 
to the parasite, if it be an insect-borne disease, and to find the 
protozoan or the bacterium which causes the disease. Both ideas 
can not be true. No theory is true which is not in accord with 
the facts. Until one of these two theories is proved or both dis- 
proved, the majority of physicians will bear to the question a 
relation of waiting. They have their opinions and are waiting for 
proof. 

The history of pellagra in other countries for the past two cen- 
turies warrants the belief that the United States is facing a long 
period during which the disease will prevail and in which many 
thousand human beings will become its victims. Little children 
will yield themselves to its insinuating and mysterious grasp ; 
strong men will become weak, and no longer able to render service 
as citizens; its mark will be left on the offspring of pellagrin 
mothers ; and especially through the southern states its ravages and 
its memory will exist side by side in every rural community. It 
has already fastened itself on the spinal cord, and its poisons flow 
in the blood of probably as many as ten thousand human beings 
in the states today. American medicine has given to the race the 
serum for the treatment of meningitis, and has discovered the in- 
sect carrier of yellow fever. There is reason to believe Ameri- 
can physicians will finally settle the problem of the cause of pel- 
lagra by the discovery and the proof of the toxin or the parasite 
which causes the disease. The corn theory is a century old and 
unproved — the infection theory of Sambon is new and unproved. 
Until the cause is definitely known, the wisdom of prophylactic 
measures is in doubt, and the hope of more satisfactory methods 
of treatment is delayed. In the language of a European physi- 
cian, "pellagra has appeared in America, and no doubt in America 
the true cause of the disease will be discovered. ' ' 



INDEX. 



Abortions in pellagra, 200 
Acidity of urine, decrease in, 197 
Acute pellagra, 83, 89 

duration of, 90 

primary, 89, 90 

secondary, 89, 90 

terminal, 89, 90 
Africa, distribution of pellagra in, 

61 
Age in relation to pellagra, 38 
Albuminuria, 198 
Alcoholic dermatosis, diagnosis of 

pellagra from, 207 
Alimentary tract in pellagra, 107 
Alkaline urine, 198 
Amebic dysentery in pellagrins, 75 
Amenorrhea, 199 

America, distribution of pellagra in, 
62 

history of pellagra in, 62 
Analysis of cases of psychosis, 178 

of corn, 234 

of stomach and intestines, 113 

of urine, 197, 198 
Anemia, 187 
Anesthesia, 203 
Ankle clonus, 163 
Ankylostomiasis in pellagrins, 75 
Antisepsis in treatment, 221 
Arsenic in treatment, 220 
Ascaris in pellagrins, 77 
Atoxyl in treatment, 221 
Atrophy, muscular, 164 
Australia, distribution of pellagra in, 

62 
Austro-Hungary, distribution of pel- 
lagra in, 59 

history of pellagra in, 59 



B 



Babinski reflex, 163 

Bacteria on corn, 241 

Bass' experiments on chickens, 264 

Bath in pellagra, 227 

Bilharziosis in pellagrins, 77 

Blood, changes in the, 185 

count, 185 

differential, 185, 186 

pressure, 189 



267 



Bones, 192 

softening of the, 192 
Bracelet, pellagrous, 131 
Brain, gross changes in the, 142 

microscopical changes in the, 143 

tissue changes in the, 142 
Buccal mucosa in pellagra, 109 
Buffalo gnat, 261 

cause of pellagra, 262 
Burning in pellagra, 137 



C 



Cachectic pellagra, 84, 93 
Cachexia in chronic pellagra, 103 
Cacodylate of soda in treatment, 220, 

222 
Cases, typical, 18 
Cataracts in pellagra, 201 
Cause of pellagra, 231 
corn as, 232, 239, 241 
good, 239 
spoiled, 241 
simulium fly as, 262 
Census of pellagrins by states, 65 
of pellagrins in Georgia, 68 
of pellagrins in Italy, 52 
Central America, pellagra in, 71 
Cerebrospinal fluid, 154 

examination of, 156 
Changes in direct pyramidal tract, 
145 
in gray matter of cord, 146 
in the blood, 185 
in the brain, 142 
gross, 142 
microscopical, 143 
tissue, 142 
in the cord, 145 
gross, 145 
microscopical, 145 
in the kidneys, 199 
in the muscular system, 164 
in the skin, 142 

in tracts of Goll and Burdach, 145 
Chickens, Bass' experiments on, 264 
Children, pellagra in, 38, 82, 250 
China, distribution of pellagra in, 62 
Chlorides in treatment, 224 
Chronic pellagra, 84, 94 

degree of desperation in, 98, 103 



268 



INDEX. 



Chronic pellagra — cont'd. 

Jansen's delineation of clinical 
course, 95 

pathology of, 118 

stages of, 97 

dyspepsia in, 98, 100 
neurasthenia in, 98, 100 
Circulatory system, 185 
Classification of pellagra, 74 
Climate, 227, 250 
Clinical symptoms, relation of cord 

lesions and 2 152 
Cod liver oil in treatment, 223 
Color of finger tips, 129 

of hands, 129 

of skin, 128 
Contagiousness of pellagra, 30, 31, 32 
Convalescent pellagra, 83, 91 
Cord, changes in the, 145 

gray matter of, 146 

gross, 145 

microscopical, 145 
Corn, analysis of, 234 

as cause of pellagra, 232, 239, 241 
good, 239 
spoiled, 241 

as diet, 226 

bacteria on, 241 

fungi on, 241, 242 

history of, 233 

in Italy, 237 

inspection of, in Italy, 52 

theory, objections to, 245 

varieties of, 233 
Cramps, 165 
Cutaneous symptoms of pellagra, 29 

D 

Definition of pellagra, 29 
Degeneracy, pellagra cause of race, 
37 

table showing race, 38 
Dementia precox type of psychosis, 

174, 176 
Dermatitis, 123, 125, 128 

color of, 128 

diagnosis before, 206 

symmetrical, 132 

treatment of, 228 
Dermatosis of pellagra, 97, 123, 126 

location of, 130 

pellagrous, 208 

relation of, to light, 133 

treatment of, 228 
Dermotagra, 123, 124, 128 
Description of pellagra, general, 29 
Diagnosis, 204 

before dermatitis, 206 

during attack of pellagra, 207 

early, 206 



Diagnosis — cont'd. 

of alcoholic dermatosis from pel- 
lagra, 207 

of erythema multiforme from pel- 
lagra, 208 

of eczema from pellagra, 208 

of sunburn from pellagra, 207 

in the intermission between at- 
tacks, 209 

without eruption, 212 
Diarrhea, 112, 116, 229 
Diet, 225 

corn as, 226 

between attacks, 225 

during attack, 225 
Differentiation of skin conditions, 207 
Digestive symptoms of pellagra, 29 
Distribution of pellagra, geographical, 
46 

in Africa, 61 

in America, 62 

in Australia, 62 

in Austro-Hungary, 59 

in China, 62 

in Egypt, 60 

in France, 53 

in Georgia, 68 

in Greece, 59 

in Italy, 48 

in Mexico, 69 

in North America, 63 

in Roumania, 59 

in South America, 71 

in Spain, 46 

in Tennessee, map showing, 54, 55 

in the world, map showing, 72, 73 

in Turkey, 59 

in United States, map showing, 
56, 57 
Duration of acute pellagra, 90 

of pellagra, 83 

of single attack, 85 
Dyspepsia in chronic pellagra, stage 
of, 98, 100 

Lauder Brunton's description of, 
107 



E 



Ears in pellagra, 202 

Ecological evidence of infection, 250 

Eczema, diagnosis of pellagra from, 

208 
Egypt, distribution of pellagra in, 60 

history of pellagra in, 60 
Egyptian synonyms of pellagra, 45 
Endemic, pellagra, 252 
English synonyms of pellagra, 45 
Environment in relation to pellagra, 

41 



INDEX. 



269 



Erythema multiforme, diagnosis of 

pellagra from, 208 
Esophagitis, 111 
Etiology of pellagra, 231 
Examination of cerebrospinal fluid, 

156, 158 
Exanthemata, pellagra sine, 104 
Eye in pellagra, 201 



F 



Families, large, limitation of pellagra 

to, 31 
Farmer, pellagra in, 26, 42 
Fever, 191 

Field laborers, pellagra in, 34 
Filiform pulse, 189 
Finger tips, color of, 129 
Fowler's solution in treatment, 220 
France, distribution of pellagra in, 
53 
history of pellagra in, 53 
French synonyms of pellagra, 44 
Fungi on corn, 241, 242 

G 

Gastric symptoms, 112 
General considerations, 17 

paralysis type of psychosis, 174, 
177 
Genito-urinary system, 197 
Geographical distribution of pellagra, 

46 
Georgia, census of pellagrins in, 68 

pellagra in, 68 
German synonyms of pellagra, 45 
Glands, salivary, 110 
Glove, the pellagrous, 133 
Goll and Burdach, tracts of, 145 
Gray matter of cord, changes in, 146 
Greece, distribution of pellagra in, 
59 

history of pellagra in, 59 
Greek synonyms of pellagra, 45 
Gums in pellagra, 109 

H 

Hair in pellagra, 134 
Hands, color of, 129 
Hearing in pellagra, 202 
Heredity in pellagra, 35, 36, 37 
History of corn, 233 
of pellagra, 46 

in America, 62 

in Austro-Hungary, 59 

in Egypt, 60 

in France, 53 

in Greece, 59 



History of pellagra — cont'd. 

in Italy, 48 

in Mexico, 69 

in North America, 63 

in Eoumania, 59 

in Spain, 46 

in Turkey, 59 
Hookworm disease, 63 

in pellagrins, 75, 77 
Housewife, pellagra in, 18 
Hydrochloric acid, lack of, 115 
Hy drothorax, 191 
Hygiene, 227 

Hymenolepis in pellagrins, 77 
Hyperesthesia, 203 



Immunity, 31, 39 

acquired, 40 

natural, 40 
Incubation period, 81 
Indigestion in pellagra, 112 
Infection, description of, 247 

ecological evidence of, 250 

of pellagra, 30 

pellagra an, 232, 247 

theory, objections to, 263 
Infections of pellagra, other, 74 
Infectious, pathological evidence that 

pellagra is, 249 
Infective exhaustive type of psychosis, 

173, 175 
Inheritance of pellagra, 35 
Insanity in pellagra, 171, 172 

pellagrous, 172, 173 

treatment of, 230 
Insect carrier, 260 
Insomnia, 166 

Intestinal parasites in pellagrins, 79 
Intestines in pellagra, 111 

analysis of, 113 
Intoxication, pellagra an, 232 
Involutional melancholia type of psy- 
chosis, 174, 177 
Italian synonyms of pellagra, 44 
Italy, census of pellagrins in, 49, 50 

corn in, 237 

distribution of pellagra in. 48 

history of pellagra in, 48 

mortality of pellagra in, 49 

prevalence of pellagra in, 49 
Itching, 136, 203 

treatment of, 228 



Jansen's delineation of clinical 
course of pellagra, 95 



270 



INDEX. 



K 

Kidneys, changes in, 199 
Knee jerks, 163 



Latency of pellagra, 40, 84, 205 
Leucorrhea, 200 

Light, relation of dermatosis to, 133 
Limitation of pellagra to large fam- 
ilies, 31 
of pellagra to rural districts, 30 
Location of dermatosis, 130 
Lungs in pellagra, 190 



M 



Mai de la rosa, 43, 122 

Malaria in pellagrins, 75 

Manic depressive type of psychosis, 

174, 176 
Map showing distribution of pellagra 
in Tennessee, 54, 55 
showing distribution of pellagra in 

the world, 72, 73. 
showing distribution of pellagra in 
United States, 56, 57 
Married woman, pellagra in, 25 
Medicinal treatment, 220 
Man, pellagra in, 33 
Menstrual period, 199 
Mental symptoms, 29, 168, 211 

summary of, 181 
Metrorrhagia, 199, 200 
Mexico, distribution of pellagra in, 
69 
history of pellagra in, 69 
Microscopical examination of cerebro- 
spinal fluid, 158 
Monkeys, experiments on, 264 
Mortality in America, 215 

in Italy, 49 
Muscular atrophy, 164 
system, changes in, 164 



N 



Nails in pellagra, 135 
Negro woman, pellagra in, 27 
Nervous symptoms, 29, 211 
summary of, 180 
system, 142 

sympathetic, 154 
treatment of, 230 
Neurasthenia, 142, 169 

in chronic pellagra, stage of, 98, 

101 
sexual, 200 
Noguchi reaction, 190 



North America, distribution of pel- 
lagra in, 63 
history of pellagra in, 63 

O 

Occupation in relation to pellagra, 40 
Onset of pellagra, 86 

diagnosis during, 206 
Outbreak of pellagra, 86 



Pain, 161 

Palate in pellagra, 109 

Panama, pellagra in, 71 

Parasites in pellagrins, intestinal, 79 

Parasitic theory of pellagra, 35 

Pathological evidence that pellagra is 

infectious, 249 
Pathology of chronic pellagra, 118 
Pelle elastica, 140 
Period of onset, 86 

of outbreak, 86 

of recession, 88 
Perspiration in pellagra, 134 
Pharyngitis, 111 
Physicians, pellagra in, 42 
Pregnancy in pellagra, 200 
Prevalence of pellagra in Italy, 49 

in Spain, 47 

in United States, 65 
Prognosis, 214 

in America, 215 

in asylums, 216 
Pronunciation of pellagra, 17 
Proportion of sex affected by pellagra, 

33 
Protozoa in pellagrins, 78 
Pseudo-pellagra, 105 
Psychosis, analysis of cases of, 178 

dementia precox type of, 174, 176 

general paralysis type of, 174, 177 

infective exhaustive type of, 173, 
175 

involutional melancholia type of, 
174, 177 

manic depressive type of, 174, 176 

senile dementia type of, 174, 177 

unclassified type of, 174, 178 
Psychoses accompanying pellagra, 171 
Ptyalism, 110 
Pulse, filiform, 189 

rate, increase in, 188 

E 

Race degeneracy, pellagra cause of, 
37 
table showing, 38 



INDEX. 



271 



Recession of pellagra, 88 
Reflex, Babinski, 163 
Reflexes, 162 

Roumania, distribution of pellagra 
in, 59 

history of pellagra in, 59 
Roumanian synonyms of pellagra, 45 
Rural disease, pellagra a, 250 

districts, limitation of pellagra to, 
30 



S 



Saliva, increased flow of, treatment 

of, 230 
Salivary glands, 110 
Salty taste in pellagra, 110 
Salvarsan in treatment, 223 
Seasons, relation of pellagra to, 80, 

250 
Senile dementia type of psvchosis, 

174, 177 
Sensory symptoms, 136 
Sex in relation to pellagra, 33 
Sexual functions, 199 

neurasthenia, 200 

organs, 199 
Simulium as cause of pellagra, 262 

fly, 261 

theory, objections to, 263 
Skin, changes in the, 138 

color of, 128 

condition, differentiation of, 207 

in pellagra, 121 
Smell in pellagra, 202 
Soamin in treatment, 221 
Sodium cacodylate in treatment, 220 
Softening of bones, 192 
Sore mouth in pellagra, 112 
South America, pellagra in, 71 
Spain, distribution of pellagra in, 46 

history of pellagra in, 46 

prevalence of pellagra in, 47 

topography of, 48 
Spanish cravat, 132 

synonyms of pellagra, 43 
Specific gravity of urine, 198 

decrease in, 197 
Stomach, analysis of, 113 

in pellagra, 111 
Stomatitis, treatment of, 229 
Streams, pellagra originates along, 

253 
Strongyloides in pellagrins, 77 
Subchronic pellagra, mild, 83, 91 

severe, 84, 93 
Sun, relation of dermatosis to, 133 
Sunburn, diagnosis of pellagra from, 

207 
Susceptibility to pellagra, 40 



Sympathetic nervous system, 154 
Symptoms, clinical, relation of cord 
lesions to, 152 
cutaneous, 29 
digestive, 29 
gastric, 112 
mental, 29, 168, 211 

summary of, 181 
nervous, 29, 211 

summary of, 180 
sensory, 136 

special, treatment of, 228 
treatment of, 219 
Synonyms of pellagra, 43 

English, 45 

Egyptian, 45 

French, 44 

German, 45 

Greek, 45 

Italian, 44 

Roumanian, 45 

Spanish, 43 



T 



Table showing census of pellagrins by 
states, 65 

showing census of pellagrins in 
Georgia, 68 

showing census of pellagrins in 
Italy, 49, 50 

showing mortality of pellagrins in 
Italy, 49 

showing race degeneracy, 38 
Taste in pellagra, 202 
Teeth in pellagra, 109 
Temperature, 191 
Tennessee, map showing distribution 

of pellagra in, 54, 55 
Tifo pellagroso, 29 
Tissue changes in the brain, 142 

in the cord, 145 
Tongue in pellagra, 108 
Touch in pellagra, 202 
Tracts of Goll and Burdach, changes 

in, 145 
Transfusion of blood, 32 

in treatment, 224 
Transmission of pellagra, 30 
Treatment, 218 

antisepsis in, 221 

arsenic in, 220 

atoxyl in, 221 

cacodylate of soda in, 220, 222 

chlorides in, 224 

cod liver oil in, 223 

Fowler's solution in, 220 

medicinal, 220 

of dermatitis, 228 

of dermatosis, 228 



272 



INDEX. 



Treatment — cont'd. 

of diarrhea, 229 

of increased flow of saliva, 230 

of insanity, 230 

of itching, 228 

of nervous system, 230 

of special symptoms, 228 

of stomatitis, 229 

of symptoms, 219 

of vertigo, 230 

salvarsan in, 223 

soamin in, 220 

transfusion in, 224 
Trichuriasis in pellagra, 77 
Tuberculosis, 190 

Turkey, distribution of pellagra in, 
59 

history of pellagra in, 59 
Typhoid pellagra, 29, 83, 89 
T3^pical cases, 18 



U 



Uncinariasis in pellagrins, 75, 77 
Unclassified type of psychosis, 174, 

178 
United States, map showing distribu- 
tion of pellagra in, 56, 57 



United States — cont'd. 

table showing census by states in, 
65 
Urine, 197 
alkaline, 198 
analysis of, 197, 198 
decrease in, 197 
acidity of, 197 
specific gravity of, 197 
specific gravity of, 198 
Urination, painful, 199 

V 

Variation in pellagra, 88 
Varieties of corn, 233 
Vertigo, treatment of, 230 



W 



Walk in pellagra, 166 
Wassermann reaction,. 190 
Weight, 193 

loss in, 193 
Widow, pellagra in, 21 
Woman, married, pellagra in, 25 

negro, pellagra in, 27 
Women, pellagra in, 33 



1 1912 



